Archive for the ‘Cancer Research’ Category
New Method Takes Aim At Aggressive Cancer Cells
Last Updated on Wednesday, 9 September 2009 10:32 Written by Editor Wednesday, 9 September 2009 10:32
A multi-institutional team of Boston-area researchers has discovered a chemical that works in mice to kill the rare but aggressive cells within breast cancers that have the ability to seed new tumors.
These cells, known as cancer stem cells, are thought to enable cancers to spread — and to reemerge after seemingly successful treatment. Although further work is needed to determine whether this specific chemical holds therapeutic promise for humans, the study shows that it is possible to find chemicals that selectively kill cancer
stem cells. The scientists’ findings appear in the August 13 advance online issue of Cell.
“Evidence is accumulating rapidly that cancer
stem cells are responsible for the aggressive powers of many
tumors,†says Robert Weinberg, a Member of Whitehead Institute for Biomedical Research and one of the authors of the study. “The ability to generate such cells in the laboratory, together with the powerful techniques available at the Broad Institute, made it possible to identify this chemical. There surely will be dozens of others with similar properties found over the next several years.â€
“Many therapies kill the bulk of a tumor only to see it regrow,†says Eric Lander, Director of the Broad Institute of MIT and Harvard, and an author of the Cell paper. “This raises the prospect of new kinds of anti-cancer therapies.â€
An emerging idea in cancer biology is that
tumors (breast, prostate, colon, lung, etc.) harbor a group of cells with the unique ability to regenerate cancers. In addition to promoting tumor growth, these so-called cancer
stem cells are largely resistant to current cancer therapies. If it were possible to identify chemicals that selectively kill cancer
stem cells, such chemicals might become critical candidates for future drug development.
However, researchers have struggled to study cancer
stem cells directly in the laboratory. The cells’ relative scarcity compared to other tumor cells, combined with a tendency to lose their stem cell-like properties when grown outside of the body, have severely limited the amount of material available for analysis.
To overcome these hurdles, Broad and Whitehead Institute researchers drew upon recent findings from Weinberg and his colleagues that suggested a way to generate in the laboratory large numbers of cancer cells with stem cell-like qualities. The technique works by coaxing adult cells to undergo a critical change (known as an “epithelial-to-mesenchymal transitionâ€) that alters their shape and motility. At the same time, the cells also adopt similar properties as
stem cells.
“A critical aspect of our work was to generate relatively homogenous and stable populations of cancer stem-like cells that could then be used for screening,†says Tamer Onder, a former graduate student in Weinberg’s lab and co-first author of the study. (Onder is now a postdoctoral
research fellow at Children’s Hospital in Boston.) “We were able to achieve this by inducing the cancer cells into an epithelial-to-mesenchymal transition using novel reagents that we had developed in the lab.â€
With an ample number of
stem cells in hand, the Broad-Whitehead team undertook a large-scale analysis of thousands of chemical compounds, applying automated methods to search for ones with activity against breast cancer
stem cells. From a pool of more than 30 promising candidates, the researchers identified a compound with surprising potency.
The compound, called
salinomycin, kills not only laboratory-created cancer
stem cells, but also naturally occurring ones. Compared to a common chemotherapeutic drug prescribed for breast cancer (known as paclitaxel),
salinomycin reduced the number of cancer
stem cells by more than 100-fold. It also diminished breast tumor growth in mice.
To further dissect the function of
salinomycin, the researchers also examined its genetic effects. Previous studies of
tumors from breast cancer patients have revealed groups of genes that are highly active in cancer
stem cells. Many of these same genes are linked with particularly aggressive
tumors and poor patient prognoses. The researchers’ studies show that salinomycin (but not paclitaxel) treatment can decrease the activity of these genes, revealing a possible molecular basis for the chemical’s biological effects.
“Our work reveals the biological effects of targeting cancer
stem cells,†says co-first author Piyush Gupta, a researcher at the Broad Institute. “Moreover, it suggests a general approach to finding novel anti-cancer therapies that can be applied to any solid tumor maintained by cancer
stem cells.â€
Although the new findings signal a noteworthy scientific milestone, it is still too early to know whether cancer patients will reap benefits from it. Additional
research is needed to determine exactly how
salinomycin works to kill cancer
stem cells and if it can wield the same tumor-reducing power in humans as it does in mice. These types of analyses generally take several years to complete.
But even with such tempered enthusiasm, there is also cause for optimism. In the current study, just 16,000 chemical compounds were tested, of which a small subset showed toxicity against cancer
stem cells. Therefore, deeper investigations of these compounds as well additional tests of broader collections of chemicals may yield other potential additions to the anti-cancer arsenal.
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Researchers develop screening test for cells that activate immune system
Last Updated on Wednesday, 26 August 2009 11:31 Written by Editor Wednesday, 26 August 2009 11:31
UT Southwestern Medical Center researchers are the first to design a large-scale, cell-based screening method that identifies which compounds activate immune-return cells that hold compact for prospective cancer-fighting vaccines.
The new screening technique can scan thousands and even millions of compounds to identify those that activate dendritic cells, which are on constant recon patrol throughout the body to scout out cancerous or infected cells and alert the immune system.
“Our assay is unique from other conventional ones in its sensitivity and cost- and time-efficiency,†said Dr. Akira Takashima, professor of dermatology and vice chairman for research and head of the project.
Dendritic cells (DCs) are considered key to developing future vaccines that can either mimic the body’s natural immune response or turn on immune responses that failed – due, for example, to cancer or an immune deficiency.
The team, which also included Dr. Norikatsu Mitzumoto, assistant professor of dermatology and the study’s lead author, and Drs. Hironori Matsushima and Hiroaki Tanaka, postdoctoral researchers in dermatology, created the cell-based biosensor system.
“We basically engineered DCs to express a fluorescent signal only when sensing activation signals so that you can identify immuno-stimulatory agents very easily,†said Dr. Takashima. Immuno-stimulatory agents launch the immune system.
The research appears on Blood magazine’s online Web site and will appear in a future issue.
“We have optimized the high-throughput screening capability – an experienced scientist can now test one thousand chemicals a day almost single-handedly,†added Dr. Mizumoto. Previously, scientists would have to test each compound individually, a time-consuming process.
Their research already has led to the discovery of several compounds that turn on dendritic cells, which are found throughout the body from skin to blood. They continuously scan the body at the cellular level looking for antigens – foreign cells and materials invading the body – and for molecular signatures of tissue damage or infection.
“Their primary job is to present antigens to the immune system so that you develop protective immunity for infection and cancer,†said Dr. Takashima.
The DC biosensor system should help pharmaceutical and biotech companies sift through large numbers of chemicals for ones that tell the dendritic cells to launch the immune response. It may also prove useful in identifying biothreat agents because it detects infectious pathogens with high sensitivity.
Dr. Takashima said he hopes to garner additional funding to discover potent immuno-stimulatory drugs by screening high-quality libraries of compounds.
Doing so may be the first step toward developing a new class of vaccines that force or trick the natural immune system to kick on, or initiate an immune response that can be copied and initiated artificially.
Other UT Southwestern researchers from dermatology involved in the study were Dr. Yasushi Ogawa, postdoctoral researcher, and Dr. Jimin Gao, former instructor.
The research was funded by the National Institutes of Health, the Dermatology Foundation Career Development Award and the American Cancer Society Junior Investigator Award.
http://www.utsouthwestern.edu/
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Southern Research to Play Key Role in the Federal Government’s Search for New Cancer Therapies
Last Updated on Tuesday, 25 August 2009 03:29 Written by Editor Tuesday, 25 August 2009 03:29
National Cancer Institute Chemical Biology Consortium to coordinate academic, private and government cancer drug discovery efforts
BIRMINGHAM, Ala., Aug. 20 /PRNewswire-USNewswire/ — Southern Research Institute today announced that it has been selected as one of 11 organizations to help establish the National Cancer Institute’s (NCI) Chemical Biology Consortium (CBC)–a program meant to coordinate and accelerate the discovery and development of new therapeutic agents to treat cancer patients. Southern Research will establish one of NCI’s five Comprehensive Chemical Biology Centers at its Birmingham campus.
“We are very pleased that Southern Research was selected to participate in this new program to expedite and coordinate the discovery and development of new cancer therapies,” said W. Blaine Knight, Ph.D., vice president of Drug Discovery and Principal Investigator of this effort at Southern Research. “Cancer accounts for nearly one out of every four deaths in this country and the National Institutes of Health estimate that the overall costs of cancer last year were more than $228 billion for health expenses and lost productivity. The search for newer and better drugs is never-ending, and something cancer patients and their families depend upon.”
Southern Research has a remarkable cancer-fighting track record having already discovered six FDA-approved drugs currently used in the treatment of cancer–amifostine, fludarabine, dacarbazine, lomustine, carmustine and clofarabine–with seven additional drugs in late stage preclinical and early clinical trials. Scientists at Southern Research have also evaluated approximately 50 percent of all FDA-approved cancer drugs currently available for patients.
“Our experience in cancer research and our track record in drug discovery were clearly recognized by our selection as a Comprehensive Center in the CBC consortium,” said John A. Secrist III, Ph.D., president and CEO of Southern Research. “We look forward to partnering with the federal government as it accelerates cancer drug discovery.”
As a Comprehensive Chemical Biology Center, Southern Research will focus on numerous aspects of preclinical drug research from target discovery, assay development, high throughput screening, structural/computational chemistry, and biology, through lead optimization and preclinical development. In addition Southern Research has an extensive compound library that will be made available for the CBC effort.
Dr. Knight says that work is expected to begin immediately.
This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Dept. of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.
About the Chemical Biology Consortium
The CBC will establish an integrated network of chemical biologists, molecular oncologists, and compound screening centers from government, academia, and eventually from industry. The drug discovery strategy of the CBC is to expand current NCI programs by providing a coordinated focus on therapeutic opportunities in high-risk, under-represented areas, significantly advancing the discovery of novel compounds active against specific molecular and genetic cancer targets. CBC efforts will include recruiting extramural investigators with specialized expertise in novel discovery platforms as well as medicinal chemistry, chemical biology, molecular oncology, and other areas of drug discovery and development. The CBC will be centrally managed to coordinate the selection of targets and screening for agents that interact with these targets, and will then use an iterative development process to design and optimize drug “hits” into “leads.” The CBC will benefit from access to the NCI’s late-stage drug development resources and expertise.
The program is being developed by NCI’s Division of Cancer Treatment and Diagnosis (DCTD), in conjunction with NCI’s Center for Cancer Research (CCR) and the NCI Director’s Office, with guidance from external advisory panels. This effort will be managed by the NCI’s Experimental Therapeutics (NExT) Program. SAIC-Frederick, Inc. (SAIC-F) will provide support for the key operational and technical aspects. It is envisioned that this Consortium will provide cutting-edge chemical tools for probing complex biochemical signaling pathways and will serve as the starting point for the elaboration of first-in-class targeted therapies. The long-term vision of the CBC is to bridge the gap between basic scientific findings and NCI-supported clinical research to facilitate the discovery and development of new agents to treat patients with cancer.
Participants will have an unparalleled opportunity to participate in a highly collaborative drug discovery partnership with the National Cancer Institute (NCI). Using state-of-the-art communication, data-sharing and project management tools, the CBC will effect a paradigm shift in the use of public-private partnerships to translate knowledge from leading academic institutions into ground-breaking new drug candidates for patients with cancer.
About Southern Research Institute
Southern Research Institute is a nonprofit 501(c)3 scientific research organization that conducts preclinical drug discovery and development, and advanced engineering research in materials, systems development, environment and energy. Our more than 550 scientific and engineering team members support clients and partners in the pharmaceutical, biotechnology, defense, aerospace, environmental and energy industries. Southern Research is headquartered in Birmingham, Ala., with facilities in Wilsonville, Ala., Anniston, Ala., Frederick, Md., and Durham, NC and offices in New Orleans, La., Washington, DC and Kiev, Ukraine. For more information about Southern Research and its capabilities and accomplishments, visit www.SouthernResearch.org.
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Vanderbilt Joins National Consortium to Develop New Cancer Therapies
Last Updated on Tuesday, 25 August 2009 03:27 Written by Editor Tuesday, 25 August 2009 03:27
Vanderbilt University has been selected as one of 10 centers in the nation to participate in the Chemical Biology Consortium (CBC), a major new initiative to facilitate the discovery and development of new agents to treat cancer.
As one of four Chemical Diversity Centers, Vanderbilt’s role in the consortium will be to synthesize and optimize new compounds as potential cancer therapeutics.
“This is a real tribute to our growth in cancer chemistry and the leverage between the Vanderbilt Institute of Chemical Biology (VICB) and the Vanderbilt-Ingram Cancer Center (VICC),†said Lawrence Marnett, Ph.D., the Mary Geddes Stahlman Professor of Cancer Research and director of the VICB.
Alex Waterson, Ph.D., research assistant professor of Pharmacology and director of the VICB’s Chemical Synthesis Core, will lead efforts developing small molecule drug candidates. Gary Sulikowski, Ph.D., Stevenson Professor of Chemistry and a co-director of the core, will direct projects involving natural products.
Designed to accelerate the discovery and development of effective, first-in-class targeted therapies, the CBC will choose high-risk targets that are of low interest to the pharmaceutical industry. The CBC is a National Cancer Institute initiative administered by contractor SAIC-Frederick, Inc.
“It’s exciting in the sense that, right off the bat, (the NCI) said that the goal of this program is to develop drugs for cancer treatment,†said Sulikowski. “They’re looking for unique targets, unique approaches, and they think that academia may offer that.â€
“Oftentimes pharmaceutical companies will not go after targets that are not expected to be huge blockbusters,†said Waterson, who came to Vanderbilt in 2008 from GlaxoSmithKline where he had worked for seven years on oncology drug development projects. “So an effort like this can fill in a niche that industry is not taking on at the moment.â€
One particular area of interest is in screening and developing natural products as potential drug candidates.
This “is something that pharmaceutical industry has de-emphasized just because of the way things have evolved,†said Sulikowski. “And that’s one of our advantages, in that we have expertise in natural products as well as medicinal chemistry.â€
Cancer drug development poses many challenges – but also unique opportunities.
“There is a difficulty in that cancer is not a single disease; it’s a family of loosely related diseases,†said Waterson. “There’s an opportunity for a whole myriad of different treatments that are pretty much only tailored to a small subset of people, where your treatment addresses their specific need.â€
A unique aspect of the CBC is the NCI’s efforts to establish intellectual property rights for investigators and institutions that develop assays or drug candidates.
“The hope is that by recognizing establishment of intellectual property as one of the goals, they will attract people with the best ideas, things that really might be able to become a drug,†said Waterson.
Vanderbilt’s involvement with the CBC, along with the recent arrival of Stephen Fesik, Ph.D., who previously led cancer drug discovery efforts at Abbott Laboratories, will make Vanderbilt “one of the best academic institutions doing cancer drug discovery in the country,†Marnett said.
Other Vanderbilt investigators involved in this effort include:
• Brian Bachmann, Ph.D., assistant professor of Chemistry and Biochemistry
• Jeffrey Johnston, Ph.D., professor of Chemistry
• Jens Meiler, Ph.D., assistant professor of Chemistry, Pharmacology and Biomedical Informatics
• Craig Lindsley, Ph.D., associate professor of Pharmacology and Chemistry, and director of Medicinal Chemistry
Other sites participating in the CBC are:
• The Burnham Institute for Medical Research, in La Jolla, Calif.;
• Southern Research Institute in Birmingham, Ala.;
• University of North Carolina at Chapel Hill;
• Georgetown University in Washington, D.C.;
• University of Minnesota;
• University of Pittsburgh;
• University of Pittsburgh, Drug Discovery Institute;
• University of California, San Francisco;
• SRI International in Menlo Park, Calif.; and
• Emory University in Atlanta
This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Source:Â vanderbilt.edu
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Killing Cancer Stem Cells
Last Updated on Tuesday, 25 August 2009 02:36 Written by Editor Tuesday, 25 August 2009 02:36
Recent evidence suggests that certain cancers may persist or recur after treatment because a small population of cells, called cancer stem cells, remains behind to seed new tumors. Though scientists are not yet certain about the role cancer stem cells play in disease, evidence is accumulating that these cells are particularly resistant to chemotherapy and radiation, and can linger in the body even after treatment.Several research groups have begun looking for substances that kill these cells. A new approach, developed by researchers at the Whitehead Institute for Biomedical Research and the Broad Institute of MIT and Harvard, makes use of high-throughput screening methods to identify chemicals that selectively target these elusive cells. In a study published today in Cell, the researchers identify one particular drug that kills breast cancer stem cells in mice. Although it is still unclear whether the drug will be useful in humans, the researchers believe their study demonstrates that it’s possible to target these cells selectively.
Because cancer stem cells, which have the ability to give rise to new tumors, may remain behind after chemotherapy and radiation treatments, finding ways to target these cells specifically may offer a way to make treatment more effective. But accessing and studying cancer stem cells has been challenging because very few are present in tumors and they are difficult to generate and maintain outside the body. Other groups have recently screened for drugs that target leukemia stem cells and brain cancer stem cells. In the Cell paper, a team led by the labs of Eric Lander at the Broad Institute and Robert Weinberg at the Whitehead Institute developed a way to generate a large number of cells that mimic naturally occurring epithelial cancer stem cells; these cells can be maintained in this state for long periods of time.
Epithelial cancers are the most common types of cancer in adults and affect the skin and inner lining of organs in the body. Using epithelial breast cancer cells, the researchers introduced a genetic change in these cells, causing them to take on the properties of mesenchymal cells, which form connective tissue in the body. Piyush Gupta, a co-author at the Broad Institute, says that for reasons not completely known, when this “epithelial-to-mesenchymal transition†is performed on breast cancer cells, it promotes the development of a large number of cells that he says are “indistinguishable from cancer stem cells.†These cells can then be grown in tiny pockets on plates and screened robotically for their response to large collections of chemicals.
The researchers used a library of 16,000 chemicals at the Broad Institute to look for compounds that killed these transformed breast cancer stem cells more effectively than they killed normal breast cancer cells. Gupta explains that since cancer stem cells are usually resistant to drugs, relatively few chemicals are effective–a mere 32 compounds were identified in the screen as preferentially treating breast cancer stem cells.
After some initial testing of several compounds, the researchers focused on one drug called salinomycin. They compared it to the actions of a drug commonly given in breast cancer chemotherapy, paclitaxel (also known by its brand name, Taxol), in cultured cells and in mice. While paclitaxel treatment leads to a higher proportion of drug-resistant cancer stem cells, salinomycin had the opposite effect, reducing the number of breast cancer stem cells in cultured cells more than 100 times more effectively than paclitaxel. The drug also reduced breast tumor growth in mice, although the reduction was less dramatic.
Gupta says that it’s not clear whether salinomycin will be a clinically useful drug, because it has not yet been tested in humans. The team is continuing to study this initial candidate drug, but he also notes, “we’re following up on several others that we think may be promising.â€
Jeffrey Rosen, a breast cancer researcher at Baylor College of Medicine, in Houston, TX, says that the study is an early example of a promising new turn in the hunt for cancer therapies. “It’s very exciting that some groups are starting not to view tumors as homogeneous entities but to target subpopulations of cells we think are import for drug resistance,†he says. However, Rosen notes that the results in mice were not as promising as the drug’s performance in cells. He says that the cancer field is hampered by a lack of good animal models to determine which drugs will be relevant for therapies. The problem, he says, is “once you pull out a compound or drug, then how do you actually go the next step and show that it’s really going to work?â€
Weinberg calls the study “the first step in the direction of trying to eliminate these cells in tumors.†He believes that even if the role of cancer stem cells in different kinds of cancer has not been resolved, “we have no doubt that getting rid of them is going to be an important part of creating cures.â€
Although this study focused on breast cancer, the researchers anticipate that the screen could be applied to any kind of epithelial cancer. Gupta says that while targeting cancer stem cells may not necessarily be a “magic bullet†in cancer treatment, “if you have a certain subpopulation of cancer cells that are resistant to standard treatment, you would want to find a compound that targets these cells.†He adds that a drug that targets cancer stem cells could be used in combination with standard treatments to ensure that resistant cells are not left behind.
Source: technologyreview.com
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Boston, MA – Drug Compound That Kills Cancer Stem Cells Identified
Last Updated on Tuesday, 25 August 2009 02:31 Written by Editor Tuesday, 25 August 2009 02:31
Boston, MA – A drug that can selectively target and kill the stem cells that drive the growth of tumors has been identified for the first time by scientists who searched more than 16,000 compounds to find it.
Researchers at Massachusetts Institute of Technology and the Broad Institute looked for compounds that could destroy the stem cells, which often resist conventional cancer treatment. One, salinomycin, cut the number of stem cells at least 100 times more than did Bristol-Myers Squibb Co.’s Taxol, a common chemotherapy medicine, according to a report on the findings published today in the journal Cell.
The researchers will conduct further testing of salinomycin in animals to assess its potential to treat humans, said Piyush Gupta, a researcher at the Cambridge, Massachusetts-based Broad Institute and co-author of the study. While the outcome of that research is unknown, he said, the work has strengthened a theory that stem cells fuel cancer and may have created a way to find effective drugs.
“We now have a method that researchers anywhere in the world can use to find agents that can kill cancer stem cells and potentially treat cancer,†Gupta said today in a telephone interview.
Stem cells appear to fuel the growth of several kinds of cancer including breast, lung and brain tumors, according to studies done in recent years. The cells are resistant to standard cancer therapy, so finding a way to thwart them is important, said Judy Lieberman, a professor of pediatrics at Harvard Medical School who researches cancer stem cells.
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‘These Are the Cells’
“These are the cells that are the important cells and if you don’t eliminate them, the tumors can grow back and recur,†Lieberman said today in a telephone interview. “Any way you can figure out to specifically target the cancer stem cells is going to fill an important gap in the therapies we have at hand.â€
Lieberman wasn’t involved in the report published today.
Scientists at universities and biotechnology companies including Infinity Pharmaceuticals Inc. of Cambridge, Massachusetts, and Australia’s ChemGenex Pharmaceuticals Ltd. are working to develop treatments to block the stem cells. Findings released in 2007 showed that one marketed anti-cancer drug, GlaxoSmithKline’s Tykerb, reduced the number of cancer stem cells and helped eliminate the disease in some breast cancer patients.
Tumor-Initiating Cells
Research by Jenny Chang at the Baylor College of Medicine has shown that after breast-cancer patients received chemotherapy and hormone treatments, the remaining tumors had a greater percentage of malignancy-initiating cells, the cancer stem cells, than before.
The researchers at MIT and Broad grew cancer cells from breast tumors in a way that increased the number of stem cells. They then used rapid screening techniques to test 16,000 commercially available chemical compounds. They identified 32 candidates before settling on salinomycin as the most potent.
They also tested the compound in mice in two ways. First, they exposed breast cancer stem cells in laboratory dishes to salinomycin and Taxol and tallied how many cells they would need to inject in a mouse to trigger a tumor. It took many more of the salinomycin-treated cells to spur cancer, showing that the compound was inhibiting cancer development, Gupta said.
Second, they induced tumors in mice and treated them with the two drugs. While both drugs exerted “significant anti-tumor effects,†the mice treated with Taxol had a greater proportion of cancer stem cells left in the remaining tumor. Taxol enriched the population of cancer stem cells and salinomycin reduced it, Gupta said.
“We have now a systematic way to look for compounds that selectively kill cancer stem cells,†Gupta said. “We’ve taken a lot of the serendipity out of the equation.â€
The research was funded partly by the National Cancer Institute.
Source: vosizneias.com
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National Cancer Institute names Emory to nationwide NCI chemical biology consortium
Last Updated on Tuesday, 25 August 2009 02:27 Written by Editor Tuesday, 25 August 2009 02:27
CBC will support rapid development of innovative, targeted cancer therapies
Emory University’s Chemical Biology Discovery Center has been selected by SAIC-Frederick, Inc. (SAIC-F) to be part of an 11-member national consortium aimed at accelerating the discovery and development of new and innovative, targeted cancer therapies. SAIC-F is the prime contractor to the National Cancer Institute at Frederick (NCI-Frederick).
The national Chemical Biology Consortium (CBC) will bridge the gap between basic scientific investigation and clinical research supported by the NCI. The consortium will focus on unmet medical needs, such as drugs that are of low interest to the pharmaceutical industry but that could have significant benefit for patients. It is expected to bring the skills of hundreds of chemical biologists, oncologists, and synthetic and medicinal chemists to bear on particularly challenging problems in molecular oncology.
Examples of the CBC’s innovative discovery pathways could include re-engineering investigators’ assays into high-throughput screens; rapidly synthesizing natural products that show promise as drug targets in a particular form of cancer; making new compounds water-soluble; and accelerating the development of drug candidates with great clinical promise.
As one of three Specialized Application Centers in the NCI Consortium, the Emory Chemical Biology Discovery Center will focus its broad capability and special expertise on protein-protein interactions in cancer through assay development and implementation, high-throughput screening, medicinal chemistry optimization and informatics, with the participation of an intellectual property specialist.
“Recent advances in our understanding of the molecular basis of cancer have led scientists to identify oncogenes and pathways involved in tumor development that offer unprecedented opportunities for innovative drug discovery,” says Haian Fu, PhD, director of the Emory Chemical Biology Discovery Center and principal investigator of the Emory CBC center. Fu is professor of pharmacology, hematology & medical oncology in Emory University School of Medicine and a co-leader of the Discovery and Developmental Therapeutics Program of the Emory Winship Cancer Institute.
“This consortium will allow the NCI and the consortium members to pursue innovative strategies and dedicate resources to interrogating new signaling pathways and promising but difficult targets for the rapid discovery and development of clinically viable new compounds that might not otherwise be developed. Examples include pediatric cancer targets,” says Fu.
The Emory center is anchored by investigators within the Emory Winship Cancer Institute and integrated with drug discovery and development capabilities of researchers throughout campus. Co-principal investigators of the Emory CBC Center are Fadlo Khuri, MD, deputy director for clinical and translational research in Emory Winship Cancer Institute and professor and chair of hematology & medical oncology, and Dennis Liotta, PhD, Emory professor of chemistry.
“Emory has a strong foundation of team science and collaboration, high throughput screening expertise and a solid record of success in the NIH Molecular Libraries Screening Centers Network,” says Liotta. “We have a team of assay biologists, screening scientists and informatics experts working side by side with medicinal chemists. Our record of drug discovery and partnerships with pharmaceutical companies show that we have the experience and expertise to serve as national leaders in cancer drug discovery.”
The Georgia Cancer Coalition (GCC) is providing matching funds for the Emory CBC Center of approximately $750,000. Emory will provide other matching funds for the Center. The Georgia Research Alliance provided initial support for the Chemical Biology Discovery Center.
“We are proud and delighted that the National Cancer Institute has once again reached out to Georgia for leadership in cancer control,” says William J. Todd, president and chief executive officer of the Georgia Cancer Coalition. “By supporting Emory’s participation in this national cancer drug discovery initiative, we are reinforcing the state’s comprehensive cancer control plan goal to accelerate improvements in cancer treatment. This designation brings us yet one step closer to making Georgia one of the nation’s premier states for cancer control.”
“As a molecular oncologist and a cancer clinician, I am very pleased with this opportunity for Emory’s involvement in a national NCI consortium to speed drug discovery,” says Khuri. “This is a very exciting time for cancer research, and I am optimistic this consortium will result in significant research advances that soon will benefit patients with particularly challenging types of cancer.”
As a member of the national consortium, the Emory center will join forces with the NCI and other national centers for project-team based accelerated cancer drug discovery operations from target identification, high throughput screening, all the way through clinical trials. It will be funded through a contractual agreement mechanism with the NCI.
In 2005 the National Institutes of Health (NIH) awarded Emory $9 million in the pilot phase of the National Molecular Libraries Screening Center Network (MLSCN). The network uses high-tech screening methods on huge libraries of small molecular compounds to identify probes as promising molecular research tools.
Emory’s CBC selection by the NCI built on Emory’s already established Chemical Biology Discovery Center and its experience in MLSCN. The Emory Chemical Biology Discovery Center is an interdisciplinary collaboration among research departments in Emory School of Medicine and Emory College. The Center also uses high-throughput technologies to screen libraries of hundreds of thousands of small molecule compounds against promising molecular targets identified by Emory scientists.
For more information about the NCI Chemical Biology Consortium: http://plan,cancer.gov./Chemical_Biology_Consortium.htm
For more information about the Emory Chemical Biology Discovery Center: http://www.emory.edu/chemical-biology/#
Emory Medicine Magazine article on drug discovery at Emory: http://whsc.emory.edu/_pubs/em/2006spring/drug_discovery.html
NIH Names Emory University a National Molecular Libraries Screening Center (press release) http://whsc.emory.edu/press_releses_print.cfm?announcement_id_seq=4040
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Forma Therapeutics, Novartis team on cancer drugs
Last Updated on Tuesday, 25 August 2009 10:31 Written by Editor Tuesday, 25 August 2009 10:31
Forma Therapeutics Inc. said that it has entered into a collaboration agreement with Novartis AG to use Forma’s cell-based screening platform to discover inhibitors for undisclosed protein-protein interaction targets to help develop cancer drugs.
No financial terms of the deal were disclosed. The funding arm of pharmaceutical giant Novartis, the Novartis Option Fund, was one of the investors in Cambridge-based Forma’s $4 million funding round in March of 2008.
Earlier this month, Forma and The Leukemia & Lymphoma Society partnered in an effort to move the health agency’s research products toward development quickly. As part of the deal, Forma will help design ten small molecule drugs using its Computational Solvent Mapping technology.
In March, Forma reported it would collaborate with the Experimental Therapeutics Centre (ETC) of Singapore on development of new anti-cancer drugs. The intent is to use Forma’s transformative chemistry platform to discover new compounds that ETC will develop.
Forma Therapeutics relies on an integrated transformative biology and chemistry-based approach to develop its drugs. It uses a cell-based screening platform to permit the screening of discrete targets in cells. Headquartered in Cambridge, Forma has research operations in Connecticut, Singapore and Beijing.
Posted under Business and Investment, Cancer Research, Compound Screening, Discoveries, Innovations and Patents, Drug Development, Industry News, Press Releases | Comments Off
SRI announces selection by the National Cancer Institute as a Chemical Biology Consortium center
Last Updated on Friday, 21 August 2009 02:19 Written by Editor Friday, 21 August 2009 02:19
Menlo Park, Calif.—July 22 , 2009—SRI International, an independent nonprofit research and development organization, announced today that SRI’s Center for Cancer Research was selected by the National Cancer Institute (NCI) for a leading role in the newly-formed “Chemical Biology Consortium” (CBC), a collaborative drug discovery partnership focused on advancing new cancer therapeutics active against novel molecular and genetic cancer targets. Based on its track record of cancer drug discovery and development, SRI was chosen to lead three of the CBC’s research and development centers: Comprehensive Chemical Biology Screening, Chemical Diversity, and Specialized Applications.
SRI has decades of experience in successfully identifying, developing and advancing novel compounds into clinical evaluation. SRI’s Center for Cancer Research, comprised of biologists and medicinal chemists with expertise in fundamental and applied cancer research, focuses on the study of tumor microenvironment, tumor metabolism, and aberrant signaling pathways that cause cancer. Through collaborative partnerships, SRI’s Center for Cancer Research has been successful in generating an extensive drug pipeline translating discoveries into beneficial treatments. SRI’s drug discovery process, guided by a combination of biological screens and computational methods, will be a key component of the NCI Chemical Biology Consortium program.
“SRI is proud to be selected to join this innovative NCI program and to continue our long-standing support of NCI’s mission to discover, develop, and bring new drugs to cancer patients,” said Lidia Sambucetti, Ph.D., senior director of SRI’s Center for Cancer Research. “Our multidisciplinary research team will bring proven expertise in fundamental and applied cancer research, backed by SRI’s fully-integrated preclinical capabilities.”
The goal of the Chemical Biology Consortium is to discover and develop new cancer therapeutics, particularly those that are beyond the scope of standard biopharmaceutical practice. The CBC will focus on therapeutic opportunities in high-risk, under-represented areas to advance the discovery of compounds active against novel molecular and genetic cancer targets.
Sambucetti will serve as the overall principal investigator of SRI’s CBC program and the Comprehensive Chemical Biology Screening Center. She will collaborate with Mary Tanga, Ph.D., an SRI senior director of medicinal chemistry, who will lead the Chemical Diversity Center, and Keith Laderoute, Ph.D., an SRI distinguished scientist, who will lead the Specialized Applications Center.
As the principal investigator of the Comprehensive Chemical Biology Screening Center, Sambucetti was invited to join the CBC Steering Committee, an NCI advisory panel that will work to ensure that CBC Centers are efficiently bridging the gap between basic scientific findings and NCI-supported clinical research.
To optimize high-quality leads and accelerate the drug discovery process, SRI will be working with BioComputing Group, Inc., a developer of computational screening, hit-to-lead, and lead optimization tools with particular emphasis on structure-guided drug discovery. These tools employ novel molecular descriptors that are derived from active compounds within the target family and from the structure of the target protein that can be applied to the evaluation of compounds from a library as well as compounds not yet synthesized. BioComputing Group, Inc. (www.BioPredict.com) has a significant track record of success in applying its tools in a hypothesis-driven paradigm to accelerate drug discovery efforts of its collaborators and clients, having placed multiple compounds into clinic with significantly reduced numbers of compounds screened and synthesized and with significantly shortened time frames.
This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-C0-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.
About SRI’s Biosciences Division
SRI International’s Biosciences Division teams with pharmaceutical and biotechnology companies, academia, foundations, and government agencies to solve important problems in global health. SRI Biosciences conducts basic research, drug discovery, and drug development, including contract research. SRI has all of the resources necessary to take R&D programs from “idea to IND”™—from initial discovery to investigational new drug applications to start human clinical trials—and specializes in cancer, immunology and inflammation, infectious disease, and neuroscience research. SRI’s internal drug pipeline has yielded several marketed drugs, several additional drugs currently in clinical trials, and more than a dozen programs in preclinical development or early discovery. In its CRO business, SRI has helped advance more than 100 drugs into clinical trials, several of which have reached the market. SRI is also working at the nexus of science and technology to create new technology platforms for the next generation of drug discovery and development in areas such as diagnostics, drug delivery, medical devices, and systems biology.
About SRI International
Silicon Valley-based SRI International is one of the world’s leading independent research and technology development organizations. SRI, which was founded by Stanford University as Stanford Research Institute in 1946 and became independent in 1970, has been meeting the strategic needs of clients and partners for more than 60 years. Perhaps best known for its invention of the computer mouse and interactive computing, SRI has also been responsible for major advances in networking and communications, robotics, drug discovery and development, advanced materials, atmospheric research, education research, economic development, national security, and more. The nonprofit institute performs sponsored research and development for government agencies, businesses, and foundations. SRI also licenses its technologies, forms strategic alliances, and creates spin-off companies. In 2008, SRI’s consolidated revenues, including its wholly owned for-profit subsidiary, Sarnoff Corporation, were approximately $490 million.
Source: www.sri.com
Posted under Cancer Research, Industry News, Press Releases, USA and Canada | Comments Off
Horizon Discovery signs screening agreement with SuperGen Inc.
Last Updated on Friday, 21 August 2009 01:04 Written by Editor Friday, 21 August 2009 01:04
Horizon’s X-MAN (Mutant And Normal) cell-line technology provides the first genetically-defined and patient-relevant in vitro models of human cancer. These models are being used by a growing number of Pharma and Biotech companies to rationalize key steps of the ‘targeted’ drug development process, and thus accelerate and economize the burgeoning field of ‘personalised’ medicine.
The agreement covers the screening of a number of lead compounds on a wide panel of human isogenic cell-lines comprising target genotypes of interest to SuperGen. The approach may enable SuperGen to gather information relating to the selectivity and mode-of-action of their compounds using model in-vitro systems.
“Dr Darrin M Disley, Commercial Director and Chairman of Horizon says “working with SuperGen is an exciting development for Horizon. In this expandable agreement, we hope to further prove the potential of our human X-MAN models in a screening environment; thus facilitating a long and productive relationship with SuperGen.â€
SuperGen will pay Horizon undisclosed fees during the term of the agreement. Work between the parties will begin in July 2009.
About Horizon Discovery
Horizon Discovery is a translational genomics company founded in June 2007 and is headquartered at the Babraham Research Campus, Cambridge, UK and with additional research laboratories in Torino, Italy. Horizon’s goal is to convert new information on the genetic causes of cancer into laboratory models that will facilitate the discovery of drugs that target these defects. Central to this aim is Horizon Discovery’s offering of X-MAN cell-lines, which represent accurate models of defined cancer patient populations and their matched normal genetic backgrounds – a missing link in the rational and efficient development of novel targeted anti-cancer agents.
Source: Cambridge Network
Posted under Business and Investment, Cancer Research, Compound Screening, Europe, Europe, Events, Industry News, Press Releases, USA and Canada | Comments Off
KINAXO’s Cellular Target Profiling® reveals mTOR as a new target of Celebrex
Last Updated on Sunday, 10 May 2009 08:46 Written by admin Sunday, 10 May 2009 08:46
Martinsried, Germany, April 29, 2009 / b3c newswire / - Kinaxo Biotechnologies GmbH has successfully applied its Cellular Target Profiling® technology to identify the protein kinase mTOR as a new cellular target of celecoxib (Celebrex®, Pfizer). Celecoxib is a non-steroidal, anti-inflammatory Cox-2 inhibitor approved for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. In addition, celecoxib’s anti-proliferative effect has earned it a place in numerous clinical trials against several malignancies.
The discovery that celecoxib targets mTOR contributes to a better understanding of the drug’s mode of action and efficacy in cancer patients. mTOR (mammalian target of rapamycin) acts as a central regulator of cell proliferation, cell survival, angiogenesis and cell metabolism. Moreover, mTOR is a key intracellular convergence point for a number of signaling pathways that are abnormally activated in many types of cancer.
As traditional drug development approaches become more and more expensive, drug repositioning has been widely recognized as an opportunity to expand a drug’s therapeutical applications. Here, Cellular Target Profiling® provides a powerful approach to revealing new targets that indicate additional or alternative medical uses for clinically validated or approved drugs. Further information on celecoxib reprofiling (AN3) and similar studies with other small molecules (e.g. profiling of the natural product geldanamycin, AN2) can be downloaded from our website at www.kinaxo.com.
Link to the news release
http://www.b3cnewswire.com/popup.php?id=149
About KINAXO
Kinaxo Biotechnologies GmbH is a privately-held biotechnology company based in Munich/Martinsried, Germany. We offer advanced chemical proteomics and phosphoproteomics services to support lead compound selection, target deconvolution, drug reprofiling, and off-target toxicity assessment. Kinaxo has several ongoing collaborations, including with Boehringer Ingelheim, Johnson & Johnson and Takeda.
Posted under Cancer Research, Drug Development, Europe, Medicinal Chemistry, Press Releases, Proteomics, Targeted Libraries | Comments Off
Molecular Fingerprints Point The Way To Earlier Cancer Diagnosis And More Targeted Treatment
Last Updated on Friday, 27 March 2009 09:52 Written by admin Friday, 27 March 2009 09:52
ScienceDaily (Mar. 27, 2009) — Metabolites are molecular fingerprints of what your cells are up to and Dr. Arun Sreekumar wants to know the impression made by cancer.
You’ve likely heard about metabolites; your physician probably screens for some known ones such as triglycerides or cholesterol at your annual physical. Scientists suspect we have about 3,000 metabolites that come from our food or are synthesized from different compounds in our bodies.
Dr. Sreekumar, a cancer researcher at the Medical College of Georgia Cancer Center, wants those screens of the blood or urine to also detect early signs of cancers such as leukemia, bladder, kidney and breast when the chance for cure is best.
He’s already begun to identify metabolites that indicate not only the presence of prostate cancer, but its aggressiveness, a tool that could help tailor optimal treatment. The search began in men at risk: those with elevated prostate specific antigen, or PSA, levels. A PSA test along with a digital rectal exam is today’s standard for prostate screening so physicians typically do both in men age 50 and older. But PSA levels are actually better at helping determine if prostate cancer has returned, Dr. Sreekumar says.
Elevated levels of PSA, a protein, are not always predictive of cancer, which means a lot of men get unnecessary biopsies. PSA measurements also can’t distinguish between tumors that have a good outcome versus those with a poor one.
“The physician does not really have the tools in hand to really say that this tumor will spread to other organs or not.” says the Georgia Cancer Coalition Distinguished Cancer Scholar. “We want to find clinical markers that supplement PSA.”
Aggressiveness is a major factor in prostate cancer treatment. In fact some men with slow growing disease likely won’t even need treatment. So he wants to provide a complement of biomarkers that accurately diagnose and categorize the disease then help monitor success of treatment. These early studies indicate a urine test may one day be possible to do just that.
He and colleagues at the University of Michigan reported in the Feb. 12 issue of Nature what appears to be one of the first metabolites implicated in cancer invasion. They looked at 1,126 metabolites in 262 samples taken from men with high PSA levels. They consistently found elevated levels of the amino acid sarcosine in the prostate tissues of men with cancer; levels were highest in what appeared to be the most aggressive tumors.
Sarcosine, a modified form of the amino acid glycine, was a known entity but its function was unclear. Scientists thought it might be a dumping ground for excess methyl groups needed to enable chemical changes of genes, proteins and other body components that can affect what and how much they do.
This process called methylation can be a good thing – like when it’s helping an embryo develop – but when it goes badly, it can cause disease such as cancer. While sarcosine’s dumping role seemed to protect from cancer, the Michigan scientists found its action actually helps induce tumors. In fact, when they added it to prostate cancer cells, the cells became more aggressive. Exactly how that process works is still under study but the findings were pretty consistent.
“When we looked at patients with metastatic disease, sarcosine levels were sky high compared to patients with localized tumors,” says Dr. Sreekumar. “It’s enabling invasion.”
Because cancer and people are both very heterogenous, measures need to be taken in larger population samples, he says. Also, they found a small group of patients with negative biopsies and high sarcosine levels. “We don’t know how many of them have missed cancer,” says Dr. Sreekumar who joined the MCG faculty in February.
These are among the reasons he believes in strength in numbers. “In the real world of biomarkers, you want 100 percent sensitivity. If the patient has cancer, you want to pick it up. We need to have a kind of multiplex test where you can test for say10 different entities and have a greater confidence that what you are stating about the tumor is true. Our goal is to develop such a panel and research on sarcosine is a first step toward achieving this.”
In his new position at MCG, he’s looking to expand the number of metabolites known to be predictive of prostate and other cancers. In prostate cancer, he’s beginning with follow up on other metabolites identified in the Michigan study in which researchers identified a total of six metabolites, including sarcosine, linked to increased tumor progression. A total of 89 metabolites were different in metastatic prostate cancer compared to localized disease.
He’s excited about what metabolites will one day tell cancer physicians and patients but adds that they are just a piece of what our bodies can tell us about a potential cancer growing inside. Scientists also need to continue to look at genes expressed by tumors and the proteins expressed by those genes to get the bigger picture. “It’s basically a systems approach you need to take,” he says.
The young scientist has worked with all those pieces in his relatively short career. He started his postdoctoral fellowship at the University of Michigan in1999, when the ability to look at gene expression was new. With his mentor, Dr. Arul M. Chinnaiyan, director of Michigan Center for Translational Pathology, Pathology Research Informatics and Cancer Bioinformatics at Michigan, he helped develop the next step: the ability to look at expression of hundreds of proteins at a time, instead of a handful, an important advance in light of the fact that there are about 1 million proteins. Recently they were among the first to venture into the world of metabolites, which are made by proteins.
“Previous technology was looking at a cell from a narrow perspective and cells never act in isolation, proteins never act in isolation, they always form complexes, act in pathways,” Dr. Sreekumar says.
His inspiration to follow those pathways is a fellow Ph.D. student who died too young and quickly of an aggressive leukemia and the fact that cancer is a leading cause of death worldwide.
Posted under Cancer Research, ChemInformatics, North America, Proteomics | Comments Off
Fruit flies soar as lab model, drug screen for the deadliest of human brain cancers
Last Updated on Saturday, 14 February 2009 02:20 Written by Editor Saturday, 14 February 2009 02:20
LA Jolla, CA—Fruit flies and humans share most of their genes, including 70 percent of all known human disease genes. Taking advantage of this remarkable evolutionary conservation, researchers at the Salk Institute for Biological Studies transformed the fruit fly into a laboratory model for an innovative study of gliomas, the most common malignant brain tumors.
“Gliomas are a devastating disease but we still know very little about the underlying disease process,” explains John B. Thomas, Ph.D., a professor in the Molecular Neurobiology Laboratory and senior author of the study, which is published in the current edition of the Public Library of Science Genetics. “We can now use the power of Drosophila genetics to uncover genes that drive these tumors and identify novel therapeutic targets, which will speed up the development of effective drugs.”
Better models for research into human gliomas are urgently needed. Last year alone, about 21,000 people in this country were diagnosed with brain and nervous system cancers, Senator Edward M. Kennedy the most famous among them. About 77 percent of malignant brain tumors are gliomas and their prognosis is usually bleak. While they rarely spread to elsewhere in the body, cancerous glial cells quickly infiltrate the brain and grow rapidly, which renders them largely incurable even with current therapies.
Gliomas originate in brain cells known as “glia” and are categorized into subtypes based on how aggressive they appear, with glioblastoma being the most common and most aggressive form of glioma. Their diversity is mirrored by the number of different signaling pathways involved in the generation of these tumors, yet aggressive gliomas all seem to have one thing in common: Most, if not all human glioblastomas carry mutations that activate the EGFR-Ras and PI-3K signaling pathways. Such mutations are also thought to play a key role in developing drug resistance.
“Fruit flies possess homologs of many relevant human genes including EGFR, Ras, and PI-3K,” explains postdoctoral researcher and first author Renee Read, who spearheaded the project. “We developed the Drosophila model to figure out how these genes specifically regulate brain tumor pathogenesis and to discover new ways to attack these tumors.”
When Read activated both signaling pathways specifically in glia in genetically engineered fruit flies, she found that, just as in the mammalian brain, activation of the EGFR-Ras and PI-3K pathways gave rise to rapidly dividing, invasive cells that created tumor-like growths in the fly brain, mimicking the human disease.
“Once I had verified that the fly tumors share key aspects with human gliomas, I could use the model to screen for new genes that are involved in disease process and compare them to the genes that were found as part of The Cancer Genome Atlas’ glioblastoma initiative,” explains Read.
Glioblastoma is one of the first cancers studied by The Cancer Genome Atlas research network, whose goal is to accelerate understanding of the molecular basis of cancer through the application of modern genome characterization technologies such as large-scale genome sequencing.
Like most cancers, gliomas arise from changes in a person’s DNA that accumulate over a lifetime but sorting changes with wide-ranging impacts from innocent bystanders has been a challenge. “While these initiatives give us big lists of altered genes they don’t tell us much about which ones are really important,” says Read. “Addressing this question in mouse models or patient studies is extremely expensive and time-consuming. In flies, I can test hundreds of genes every week.”
The Salk researchers are now using their fly model to search for genes and drugs that might block EGFR/PI-3K-associated brain tumors. The drug tests are being done in collaboration with co-authors professor Webster Cavenee, Ph.D., and associate professor Frank Furnari, Ph.D., both experts in human brain tumor biology at the Ludwig Institute for Cancer Research at the University of California, San Diego.
The researchers are hoping that through their combined efforts new discoveries from the fly model can be rapidly translated into mouse and human brain tumor studies and lead to development of new therapies for this deadly cancer.
Posted under Cancer Research, Discoveries, Innovations and Patents, North America, Press Releases, Research Projects, USA and Canada | Comments Off
CytRx Unveils Clinical Development Plan for Pipeline Assets
Last Updated on Friday, 12 December 2008 02:47 Written by Editor Friday, 12 December 2008 02:47
Names World-Renowned Cancer Drug Expert Dr. Joseph Rubinfeld as Chief Scientific Advisor
LOS ANGELES–(BUSINESS WIRE)–CytRx Corporation (NASDAQ: CYTR) today unveiled its corporate strategy to focus its internal resources on the clinical development of oncology drug candidates tamibarotene and INNO-206, which the Company believes offer the greatest mix of near-term and medium-term revenue potential among its clinical assets. CytRx will pursue partnerships to advance the clinical development of INNO-406 (bafetinib) and its clinical molecular chaperone portfolio, where it continues to see significant future revenue potential. The Company further intends to use its proprietary high-throughput, high-content drug screening Master Chaperone Regulator Assay (MaCRA) platform to discover additional molecular chaperone drug candidates, including those that may inhibit cancer growth, which will support internal efforts to build an oncology drug franchise or future out-licensing possibilities.
CytRx also announced that Board of Directors’ member Dr. Joseph Rubinfeld has accepted the additional responsibility of Chief Scientific Advisor, and will consult on all aspects of the Company’s oncology development programs while serving as an important interface between the Company and investors, clinicians and industry thought leaders. Dr. Rubinfeld brings substantial expertise in oncology and drug development through his distinguished career. Dr. Rubinfeld was employed at Bristol-Myers Company International Division as Vice President and Director of Research and Development. While at Bristol-Myers, Dr. Rubinfeld was instrumental in licensing the original anticancer line of products, including Mitomycin and Bleomycin. Among other accomplishments, he was among the four co-founders of Amgen, Inc., and founded SuperGen, Inc., where he previously served as CEO, President and Chief Scientific Officer. In his career he has been instrumental in the development of several blockbuster cancer drugs including cisplatinum, etoposide, erythropoietin, decibitene and pentostatin, and the antibiotics amoxicillin and cefadroxil.
Steven A. Kriegsman, CytRx President and CEO said, “We feel that our stockholders are best served by a focus on potential therapeutics for cancer. We believe tamibarotene has strong potential as a revenue generator with a high likelihood for rapid U.S. approval as a third-line treatment for acute promyelocytic leukemia (APL). Our view is based on the substantial clinical history of tamibarotene as an approved treatment of relapsed APL, in Japan and the existing special protocol assessment (SPA) in place with the U.S. Food and Drug Administration (FDA) for our ongoing U.S. registration clinical trial. We are accelerating enrollment in this clinical trial, with the expectation of filing an NDA with the FDA as early as 2010. We are also taking steps to move into a Phase 2 clinical trial with INNO-206, our highly promising targetable pro-drug for the commonly prescribed chemotherapeutic doxorubicin. We believe that INNO-206 could be effective in a wide variety of cancers, including small cell lung cancer, sarcoma, breast and ovarian cancer and Non-Hodgkins Lymphoma.
“Importantly, we expect that we have ample financial resources with our current cash position and investment in RXi Pharmaceuticals Corporation to support this strategy,†according to Mr. Kriegsman. “We have strong oncology expertise within CytRx and are delighted that Dr. Joseph Rubinfeld, our long-time board member who has enjoyed an illustrious career developing cancer drugs, will be taking a leadership role in our oncology programs.â€
Dr. Rubinfeld said, “Having reviewed the extensive data on tamibarotene and INNO-206, I am excited about the potential for these two cancer drug candidates and look forward to working closely with the CytRx management team to advance their clinical development to potential commercialization. I am also encouraged by the Phase 1 data we announced earlier this month with INNO-406, now known as bafetinib, which demonstrated positive, clinical responses in 35% of patients with refractory chronic myeloid leukemia. I believe these results will be instrumental in our search for a partnership for bafetinib.â€
Mr. Kriegsman added, “We also stand behind our view that our orally administered molecular chaperone drug candidates, arimoclomol and iroxanadine, provide enormous potential in addressing large, underserved markets and are convinced that the prudent course to maximize stockholder value in this economic climate is to pursue pharmaceutical partners to share additional development costs for these longer-term programs. We intend to complete our ongoing arimoclomol animal toxicology studies and work aggressively toward lifting the current clinical hold in order to enable this drug candidate to move back into the clinic. At that point, we will seek partners for further development of arimoclomol as a therapeutic treatment for both ALS and stroke recovery. Additionally, iroxanadine has shown significant potential as a therapeutic treatment for diabetic foot ulcers and other diabetic complications, and based on Phase 2 data, we will pursue potential partnerships in cardiovascular conditions.â€
CytRx’s drug portfolio includes the following:
Oncology Drug Candidates:
Tamibarotene: CytRx holds the North American and European rights to tamibarotene, a rationally designed, synthetic retinoid compound designed to potentially avoid toxic side effects of the current first-line APL treatment trans-retinoic acid (ATRA). CytRx is actively enrolling patients in a Phase 2 registration clinical trial, known as STAR-1, with tamibarotene to evaluate its efficacy and safety as a third-line treatment for APL. The registration study is being conducted under a Special Protocol Assessment. The FDA has granted Orphan Drug Designation and Fast Track Designation for the use of tamibarotene in patients with relapsed or refractory APL following treatment with ATRA and arsenic trioxide.
There are currently no approved third-line treatment options for refractory APL patients. CytRx estimates the U.S. market opportunity for tamibarotene in refractory APL at approximately $20 million annually. CytRx scientists are also evaluating clinical strategies for developing tamibarotene as a first-line or second-line APL therapy. The estimated annual market potential in the U.S. and Europe for an expanded label including refractory, maintenance and front-line therapy is $150 million. CytRx also retains an option to expand its licenses for the use of tamibarotene in other cancers including multiple myeloma, myelodysplastic syndrome and certain solid tumors in the U.S., and multiple myeloma, myelodysplastic syndrome and solid tumors, other than hepatocellular carcinoma, in Europe.
INNO-206: This pro-drug derivative of the commonly prescribed chemotherapeutic agent doxorubicin is designed to reduce adverse events by controlling drug release and preferentially targeting the tumor. In a Phase 1 study, INNO-206 was administered in doses at up to six times the standard dosing of doxorubicin without an increase in observed side effects over those historically seen with doxorubicin. Objective clinical responses were seen in patients with sarcoma, breast and lung cancers. The Company plans to evaluate further clinical development of INNO-206 in a wide variety of cancers, including sarcomas, breast and ovarian cancer, and Non-Hodgkins Lymphoma.
INNO-406 (bafetinib): INNO-406 (bafetinib), a potent, orally available, rationally designed, dual Bcr-Abl and Lyn-kinase inhibitor, is being evaluated for the treatment of patients with chronic myeloid leukemia (CML) and other leukemias that have a certain mutation called the Philadelphia Chromosome (Ph+) and are intolerant of or resistant to imatinib (Gleevec®) and second-line tyrosine kinase inhibitors (i.e. dasatinib (Sprycel®) and nilotinib (Tasigna®)). In November 2008, CytRx announced that bafetinib demonstrated positive, clinical responses in 35% of patients with CML in Phase 1 clinical testing. The Phase 1 clinical trial was used to determine the optimal dose prior to Phase 2 clinical efficacy testing.
CML is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. In 2007, the American Cancer Society estimated that approximately 4,600 new cases of CML were diagnosed in the U.S. and that the number will increase as the population ages. Current estimates are that worldwide CML prevalence will increase by 10,000 patients a year, reaching a population of 110,000 in 2010. The global market will grow to an estimated $5.5 billion by 2012.
Molecular Chaperone Regulation
CytRx is a leader in molecular chaperone regulation technology. The Company currently has two orally administered, clinical-stage, drug candidates and recently discovered a series of additional compounds that may provide a pipeline for additional drug candidates. The Company’s drug candidates are believed to function by regulating a normal cellular protein repair pathway through the activation or inhibition of “molecular chaperones.” Because damaged proteins are thought to play a role in many diseases, activation of molecular chaperones that help to reduce the accumulation of misfolded proteins may have therapeutic efficacy in a broad range of disease states. Similarly, CytRx believes that the inhibition of molecular chaperones that normally help protect cancer cells from toxic misfolded proteins may result in the selective destruction of cancer cells.
- Arimoclomol: This molecular chaperone regulator drug candidate is being considered as a treatment for amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) and stroke recovery. Arimoclomol has been studied in seven Phase 1 and two Phase 2 clinical trials without any significant adverse events. CytRx’s Phase 2b clinical trial with arimoclomol as a treatment for ALS was placed on clinical hold by the FDA in January 2008, unrelated to any data generated by human studies, and additional preclinical toxicology studies are underway to resolve this issue.
- Iroxanadine: CytRx believes that this orally available small molecule compound represents a potentially powerful breakthrough in the treatment of vascular diseases that are caused in part by damage to “vascular endothelium” that lines the inside of blood vessels. CytRx believes that endothelial dysfunction plays a key role in the development of various vascular diseases or their complications including diabetic ulcers, thrombosis, retinopathy, and peripheral artery disease. Preclinical and clinical studies with iroxanadine indicate that it has therapeutic potential for the treatment of cardiovascular atherosclerosis. According to the National Heart, Lung & Blood Institute, atherosclerosis is a leading cause of illness and death in the U.S. and affects approximately 4.6 million people annually.
CytRx San Diego Laboratory: The CytRx San Diego Laboratory is using the Company’s proprietary Master Chaperone Regulator Assay (MaCRA), a cell image-based screening tool that enables the rapid and quantifiable screening of large numbers of small molecule compounds. This technology is used to identify potential drug candidates that modify the activity of a protein known as heat shock transcription factor 1 (Hsf1) and consequently control entire groups of molecular chaperone proteins that repair or degrade toxic misfolded proteins present in diseased cells. Evaluation of the compounds identified in the screen has shown that they exhibit cytoprotective properties in cell culture models of disease. This platform has broad applicability to a range of therapeutic areas, through its ability to identify drug candidates that can either inhibit or amplify molecular chaperone activity. Information related to the development of MaCRA for compound screening was published in the November 2008 issue of the peer-reviewed Journal of Biomolecular Screening.
CytRx Oncology Expertise
Collectively, CytRx’s management and its Board of Directors have brought numerous cancer drugs to market. In addition to Dr. Rubinfeld, the senior managers and directors of CytRx who hold significant oncology experience include: Max Link, Ph.D., Chairman of the Company’s Board of Directors since 1996, who served for a number of years as Chairman and CEO of Sandoz Pharma as well as a director of Alexion Pharmaceuticals, Inc., Celsion Corporation and Discovery Laboratories, Inc.; Jack R. Barber, Ph.D., Chief Scientific Officer, who has significant R&D experience in oncology at Immusol and Viagene, where he most recently served as Head of Oncology; and Shi Chung Ng, Ph.D., Senior Vice President of Research and Development, who has substantial R&D experience at companies such as Abbott and ArQule, Inc., and most recently served as Vice President of Molecular Oncology at Ligand Pharmaceuticals.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and development company engaged in the development of high-value human therapeutics. The CytRx drug development pipeline includes programs in clinical development for cancer indications, including tamibarotene in a registration study for the treatment of acute promyelocytic leukemia (APL). CytRx is developing two drug candidates based on its industry-leading molecular chaperone technology, which aims to repair or degrade misfolded proteins associated with disease. The Company owns and operates a research and development facility in San Diego. CytRx also maintains a 45% equity interest in publicly traded RXi Pharmaceuticals, Inc. (NASDAQ: RXII). For more information on the Company, visit www.cytrx.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including risks relating to the outcome or results of any pre-clinical or clinical testing of CytRx’s potential oncology or molecular chaperone drug candidates, including tamibarotene as a third-line treatment for APL, risks related to CytRx’s ability to enter into partnerships to advance the clinical development of INNO-406 and its clinical molecular chaperone portfolio, uncertainties related to the impact of the FDA’s clinical hold on the Company’s arimoclomol clinical trial for ALS on the timing and ability to resume clinical testing at the desired dosage of arimoclomol, the risk that any requirements imposed on the Company’s planned clinical trial designs for ALS or stroke recovery by the FDA as a result of the concerns expressed in their clinical hold of the Company’s ALS program might adversely affect the Company’s ability to demonstrate that arimoclomol is efficacious in treating ALS or stroke patients or cause the Company to cancel one or both of those trials, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, risks related to the future market value of CytRx’s investment in RXi and the liquidity of that investment, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
The German Cancer Research Center Investigates the Role of miRNAs in Carcinogenesis Using febit’s Geniom RT Analyzer
Last Updated on Friday, 24 October 2008 02:14 Written by admin Friday, 24 October 2008 02:14
LEXINGTON, Mass. (USA), and HEIDELBERG, Germany, Oct. 20, 2008 – The German Cancer
Research Center, also known as DKFZ, in Heidelberg (Germany) chose febit´s newly
introduced Geniom® RT Analyzer to investigate the association of microRNAs (miRNAs)
and cancer.
miRNAs are small pieces of RNA with a maximum length of 23 nucleotides, which have
become an important focus of life-science research in the past couple of years.
Since they do not encode any proteins, they remained largely unappreciated for many
decades. Recently, however, scientists began to realize their crucial role in the
regulation of intracellular events such as differentiation or apoptosis of cells.
The number of miRNA being discovered is growing by the day.
DKFZ scientists therefore searched for a technology that would allow them to keep
pace with the rapidly evolving miRNA databases, continually incorporating the latest
information into their research on the role of miRNAs in carcinogenesis. The newly
developed Geniom RT Analyzer ideally meets this requirement: it exploits freely
configurable biochips produced on demand at febit for microarray analysis of miRNA
profiles in biological samples.
“Our positive experience with the flexibility of febit´s Geniom contributed to our
decision to use the new Geniom RT Analyzer,” said Joerg Hoheisel, director of the
DKFZ Functional Genome Analysis Division. “Preliminary tests indicate an excellent
quality of microarray analysis. In addition, my team is enthusiastic about the
straight-forward operation and outstanding efficiency of the instrument.”
In addition to flexibility, the Geniom RT Analyzer offers a high degree of
automation and numeÂrous user-friendly features: all steps in the workflow,
including sample addition, hybridization, staining, washing, shaking and detection,
are performed in one single instrument requiring a minimum of operator time. The
efficient operation results with minimal error rates and offer consistent
experimental parameters providing highly reproducible results. Data read out by the
Geniom Wizard software may then be analyzed with standard software solutions.
In addition to miRNA analysis, the Geniom RT Analyzer offers a variety of other
high-performance applications. For example, a patented biochip protocol enables the
fragmenÂtation and sorting of large genomes in smaller well-defined fractions.
Without this essential fractionation step, the complexity of the genomic DNA would
preclude any effective analysis. These may then serve as samples in mutation
analysis and high-throughput sequencing with next-generation sequencers.
febit’s new Geniom RT Analyzer combines extraordinary flexibility with a high degree
of automation for microarray analysis. (Photo: febit)
About febit
febit enables scientists to read, write and understand the code of life: DNA. With
its unique Geniom technology and services, febit is the only company that puts the
control of simplified genomic research in the hand of the user. The seamless
integration of DNA synthesis and analysis and the superior support in experiment
design and bioinformatics helps to understand data and turn it into results. febit’s
team of experienced scientists is dedicated to support customers to solve the
challenge of understanding biological processes. Geniom is a technological and
service platform successfully implemented in basic and applied research by renowned
institutions and companies. Geniom exploits cutting-edge microarray technology for
analysis and synthesis of genes and genomes, providing superior time- and
cost-efficiency combined with an unsurpassed spectrum of applications.
For more information about febit and its products please visit
www.febit.com
About the DKFZ, Division of Functional Genome Analysis
Research at the division of Functional Genome Analysis at the DKFZ (German Cancer
Research Center) aims at the development and immediate application of new
technologies for the production and processing of molecular information at a global
cellular level. The overall objectives are an analysis, assessment and description
of the realisation of cellular function from genetic information as well as the
understanding of the regulation of the relevant processes. Many projects are pursued
in national and international collaborations and programmes.
For more information on Functional Genome Analysis at the DKFZ, please visit
www.dkfz.de/funct_genome/
Posted under Cancer Research, Collaborations, Europe, Genomics & Pharmacogenomics, Press Releases, RNA Reasearch | Comments Off
deCODE and Radboud University Discover Common Variants in the Human Genome Conferring Risk of Bladder Cancer
Last Updated on Wednesday, 17 September 2008 01:47 Written by Fred Wednesday, 17 September 2008 01:47
Detection may be used to complement and target screening for the disease; findings will be integrated into the deCODEme(TM) personal genome scan.
Last update: 1:30 p.m. EDT Sept. 14, 2008
REYKJAVIK, Iceland, Sept 14, 2008
DCGN and colleagues at Radboud University Medical Center in the Netherlands today report the discovery of two common single-letter variants in the human genome (SNPs) that confer increased risk of urinary bladder cancer. Approximately 20% of people of European descent carry two copies of the first variant, a version of a SNP on chromosome 8q24, putting them at a 50% higher risk of developing bladder cancer than those without the variant. Individuals who carry two copies of a common version of another SNP on chromosome 3 were found to be at a 40% higher risk of the disease than non-carriers. These are the best-replicated genetic variants ever linked to bladder cancer risk, and the study analyzed genotypic data from more than 40,000 patients and controls from Iceland, the Netherlands and eight other European countries. The paper, entitled ‘Sequence variant on 8q24 confers susceptibility to urinary bladder cancer,’ will appear today in the online edition of Nature Genetics at www.nature.com/ng.
“In all cancers, the ability to identify individuals at high risk, screening them intensively and intervening early, is the key to improving prevention and outcomes. We expect that the detection of these and other risk variants will soon be employed to complement the assessment of standard risk factors for bladder cancer. As with all of our discovery work, we seek to publish our findings and establish a solid intellectual property position in order to bring these swiftly into the healthcare arena, and have already folded today’s findings into our deCODEme(TM) personal genome analysis service. At the same time, we are working to identify the common thread of variants we and others have discovered on chromosome 8q24 that confer risk of several forms of cancer, including prostate, breast, colorectal and now bladder. If a common molecular mechanism exists, it could provide an important insight into oncogenesis more broadly,” said Kari Stefansson, CEO of deCODE.
For a more detailed discussion of today’s findings you can watch a video discussion between Dr. Stefansson and Dr. Simon Stacey on our blog, at www.decodeyou.com.
Urinary bladder cancer is the sixth most common type of cancer in the United States. It is estimated that 68,810 individuals will be diagnosed with bladder cancer in the United States during 2008 and that 14,100 people will die of the disease. Bladder cancer has been linked to exposure to various types of toxic substances such as cigarette smoke and industrial chemicals. Although it has been known for some time that genetic factors also play a significant role, identifying validated genetic risk variants had been problematic. Incidence of bladder cancer varies considerably between ethnicities, and as the risk factors reported here were discovered by analyzing DNA from groups of European descent, it is our hope that the publication of these findings will contribute to the swift analysis of the impact of these variants in cohorts of other continental ancestries.
The authors wish to thank the thousands of patients and control subjects who participated in this study, and acknowledge the assistance of national cancer registries that worked to identify potential participants. Data and sample collection in Iceland and the Netherlands was funded in part by European commission grants LSHC-CT-2005-018827 and LSHM-CT-2004-005166.
About deCODE
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of diagnostics and drugs for common diseases. deCODE is a global leader in gene discovery — our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. Through its CLIA-registered laboratory, deCODE is offering a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2(TM) for type 2 diabetes; deCODE AF(TM) for atrial fibrillation and stroke; deCODE MI(TM) for heart attack; deCODE ProCa(TM) for prostate cancer; and deCODE Glaucoma(TM) for a major type of glaucoma. deCODE is delivering on the promise of the new genetics.(SM) Visit us on the web at www.decode.com; on our diagnostics site at www.decodediagnostics.com; for our pioneering personal genome analysis service, at www.decodeme.com; and on our blog at www.decodeyou.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results, and the timing of events, to differ materially from those described in the forward-looking statements. These risks and uncertainties include, among others, those relating to our ability to obtain financing and to form collaborative relationships, uncertainty regarding potential future deterioration in the market for auction rate securities which could result in additional permanent impairment charges, our ability to develop and market diagnostic products, the level of third party reimbursement for our products, risks related to preclinical and clinical development of pharmaceutical products, including the identification of compounds and the completion of clinical trials, the effect of government regulation and the regulatory approval processes, market acceptance, our ability to obtain and protect intellectual property rights for our products, dependence on collaborative relationships, the effect of competitive products, industry trends and other risks identified in deCODE’s filings with the Securities and Exchange Commission, including, without limitation, the risk factors identified in our most recent Annual Report on Form 10-K and any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.
Posted under Cancer Research, Discoveries, Innovations and Patents, Europe, Press Releases | Comments Off
Colon Cancer Oncogene Discovered
Last Updated on Wednesday, 17 September 2008 01:30 Written by Fred Wednesday, 17 September 2008 01:30
SUNDAY, Sept. 14 (HealthDay News) — Researchers have identified a new genetic player in the development of colon cancer.
The findings implicate CDK8, a protein that regulates gene expression in the proliferation of colorectal cancer, the researchers found.
Should the results be validated, they could lead to new therapeutic approaches for colon cancer, as well as new screening and chemopreventative strategies, said Dr. Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society.
“I think it is important work,” Brooks said. “They have identified what apparently is an oncogene associated with some colorectal cancers.”
Dr. William Hahn, of the Dana-Farber Cancer Institute in Boston, and his colleagues screened human colon cancer cells for genes that met three criteria: They were required for cellular proliferation, critical to regulating the WNT/beta-catenin signaling pathway known to be involved in the bulk of colon cancer cases, and also genetically amplified in cancerous cells.
“When we did that, we found one gene that fulfilled all three criteria, and that is CDK8,” Hahn said.
The results were published in the Sept. 14 issue of Nature.
CDK8 is a member of the so-called mediator complex, which bridges distant protein complexes to activate expression of certain genes.
According to Hahn, the study has two take-home messages.
The first, he said, is the apparent prevalence of colorectal tumors with elevated CDK8. Of the 50 tumors that Hahn and his team analyzed, 31 (62 percent) displayed evidence of CDK8 gene amplification — that is, the tumors contained more than the normal two copies of the gene, which usually leads to higher levels of protein expression.
“This is surprising in the sense that it occurs in a large percentage of colon cancers, and we didn’t know about it,” he said.
The second message involves the potential pharmacologic benefits of these results. CDK8 is a type of protein known as a kinase. Kinases are enzymes that catalyze the transfer of phosphate groups from one molecule to another. That action is like flipping a molecular switch, causing the recipient protein to turn on or off. It turns out that kinases tend to play key roles in the biochemical pathways that often go haywire in cancer, so they are popular targets for drug developers.
“There’s a reasonable likelihood, though it hasn’t happened yet, that one could develop a drug that targets this protein in colon cancer,” he said, “and you could determine which colon cancer patients are likely to benefit.”
That’s because Hahn and his team showed, using a genetic technique called RNA interference, that knocking down CDK8 protein levels in cancer cells that normally contain elevated CDK8 levels, reduced cell proliferation. That effect was less pronounced in cells containing lower levels of CDK8.
So, those tumors with elevated CDK8 levels might make good candidates for novel drug therapies directed at the enzyme, Hahn said.
“This fits into an emerging concept in cancer treatment,” he explained. “Not only do we develop better therapies, but hand-in-hand, we want to find which patients will respond to therapy, rather than giving it to everyone and hoping they will respond.”
Brooks agreed that CDK8 is a potential drug target. He noted other potential benefits, too, such as possibly being able to identify those at elevated risk of developing colorectal cancer, or identifying those who should be screened earlier and more comprehensively. It may even be possible to develop chemopreventative compounds that could diminish the risk of developing cancer in the first place.
“But we are at the very beginning of that pathway,” Brooks added. “All they have shown is this oncogene seems to be associated with a significant number of cancer specimens…. But translating that to, number one, how broadly this occurs in the broader community of colorectal cancer, and also in the general patient population, and then next, how can we use this information, we are at the very beginning of that process.”
In another report in this week’s online issue of Nature Genetics, researchers from Iceland said that they have found a genetic variant associated with increased risk of urinary bladder cancer.
Posted under Cancer Research, Discoveries, Innovations and Patents, North America, Press Releases | Comments Off
TOCRIS SIGNS EXCLUSIVE DEAL TO SUPPLY GEFITINIB
Last Updated on Thursday, 4 September 2008 03:20 Written by admin Thursday, 4 September 2008 03:20
September 4th, 2008 – Tocris Bioscience announced today the signing of an exclusive deal with AstraZeneca to supply Gefitinib (also known as Iressa and ZD1839) to preclinical researchers working on the mechanisms underlying cancer development. For the first time, scientists will be able to buy authentic, fully licensed, non-formulated Gefitinib as an off-the shelf product for use in biological research.
In recent years pharmaceutical companies have developed a number of small molecule drugs that are clinically effective against certain types of cancer. Tyrosine kinase inhibitors (TKIs) such as Gefitinib are at the forefront of this new generation of targeted anticancer agents.
Gefitinib is an EGFR-TKI (epidermal growth factor tyrosine kinase inhibitor), which targets and blocks the activity of the EGFR-TK, an enzyme that regulates intracellular signalling pathways implicated in cancer cell proliferation and survival. Growth factor signalling has been identified as a key driver of tumour growth and spread in a wide range of cancers. For clinical use, Gefitinib has been approved for the treatment of advanced Non Small Cell Lung Cancer (NSCLC) in 36 countries.
This molecule has been licensed to Tocris for use as a preclinical research compound only. Strict conditions have been imposed by AstraZeneca to ensure that it is not used in human studies.
Duncan Crawford, Tocris’ Chief Scientific Officer, said, “We know that there is a great deal of interest in Gefitinib from the global research community. By making fully licensed Gefitinib available through our catalogue, we hope to promote new and exciting research in the fundamental processes that drive cancer development. For Tocris this important new product perfectly compliments our comprehensive and expanding range of high purity compounds, which are in use worldwide to further biomedical research. We are delighted that our excellent relationship with AstraZeneca has allowed us to make this compound available to scientists working on the fundamental mechanisms of cancer cell biology”
About Tocris Bioscience
Tocris Bioscience is a leading supplier of high performance chemicals, peptides and antibodies, with customers in virtually all of the world’s major pharmaceutical companies, universities and research institutes. The Company is committed to making new life science discoveries possible by providing the highest performing and most innovative range of research reagents.
Tocris Bioscience products are used by scientists carrying out non-clinical research in fields such as cancer, stroke, Alzheimer’s disease and obesity. The Company’s product range of over 2,000 reagents represents a unique collection of novel, exclusive and licensed research tools. A major source of key signal transduction reagents and arguably the world leader in the supply of neuroscience reagents, the Company won the Queen’s Award for Enterprise (International Business) in 2002.
Tocris Bioscience is the trading name for the companies in the Tocris Cookson Group. Formed from the 1994 merger of Tocris Neuramin and Cookson Chemicals, Tocris Cookson Ltd is privately held and headquartered in Bristol, UK. Its US subsidiary, Tocris Cookson Inc, is located in St. Louis, Missouri, USA. There are approximately 50 employees in the Group worldwide, operating out of two sites in the UK and one in the US.
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world’s leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit: www.astrazeneca.com
Posted under Cancer Research, Collaborations, Compound Libraries, Drug-Like Compounds, Europe, Press Releases, Targeted Libraries | Comments Off
New drug slows down cancer
Last Updated on Tuesday, 2 September 2008 11:44 Written by Fred Tuesday, 2 September 2008 11:44
WA researchers have taken the first step towards developing new anti-cancer medications that could activate a gene shown to block the growth of cancerous cells.
Led by Western Australian Institute for Medical Research (WAIMR) Director Professor Peter Klinken, the scientists have screened a large collection of drug-like molecules and recently identified a number of compounds which can increase levels of the Hls5 gene.
“This discovery is very encouraging and a great step forward in our quest to create new cancer treatments,” said Professor Klinken.
“Because of the role Hls5 plays in keeping cell growth at a normal rate, we expect that these compounds will greatly slow down the growth of cancer cells.”
The Hls5 tumour suppressor gene was reported by Professor Klinken’s team in 2004.
The group’s research has revealed that people who don’t have the gene – or those who have a mutated or inactive form of the gene – are more likely to develop certain types of cancer.
In conjunction with WA-based biotechnology company BioPharmica, the WAIMR team has spent more than a year screening 70,000 compounds which increase Hls5 levels.
“Our preliminary data reveals that several of these compounds do indeed markedly slow down the growth of human cancer cells,” said Professor Klinken.
“Importantly, we also know through computer modeling that nearly all of these compounds have drug-like qualities.”
“From here, we take the research to the next phase of laboratory testing with the ultimate hope of investigating if one of these molecules can be used to create a fresh treatment that can slow growth of cancer cells in patients.”
Posted under Cancer Research, North America, Press Releases | Comments Off
AstraZeneca, Singapore institutions sign innovative new partnership to develop anti-cancer compounds
Last Updated on Tuesday, 19 August 2008 03:19 Written by Fred Tuesday, 19 August 2008 03:19
Healthcare company AstraZeneca Plc (AZN: News, Chart, Quote ,AZN.L: News, Chart, Quote ) said Friday that it signed an innovative new partnership with the National Cancer Centre Singapore, or NCCS, and the National University Hospital, or NUH, for development of anti-cancer compounds. The collaboration is spelt out in a Memorandum of Understanding, or MOU.
As per the MOU, AstraZeneca and the Singapore institutions will enter into a collaborative agreement that spans both clinical and pre-clinical development activities.
AstraZeneca noted that the partnership also includes a Training Programme placement with the Manchester Cancer Research Centre, with whom AstraZeneca has a formal research alliance. Singapore Economic Development Board partly supports the training programme. The purpose of the training programme is to train a pool of clinical research professionals for both private-sector and public-sector research labs.
According to AstraZeneca, the partnership aims to further build its drug development capabilities in Asia and ultimately accelerate access to new medicines of potential benefit to patients with inoperable Hepatocellular Carcinoma, or HCC. HCC is a cancer that is particularly prevalent in Asia and accounts for approximately one million deaths annually worldwide.
Under the terms of the clinical development collaboration, NCCS and NUH can access AstraZeneca compounds that have already undergone initial clinical testing in the West.
The institutions have already identified AstraZeneca’s two compounds for clinical screening in inoperable HCC during 2008 and 2009. The company stated that more compounds would be made available at a rate of one per year, for the duration of the partnership, which exists until 2012.
For both clinical and pre-clinical activities, AstraZeneca maintained the alternative to presume further development and marketing of all drugs made available as part of the partnership deal.
AZN closed Thursday’s regular trade at $49.04, up $0.34, on a volume of 1.2 million shares.
Posted under Asia, Asia, Cancer Research, Collaborations, Press Releases | Comments Off
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