Archive for the ‘Oncology Research’ Category

Using SPA to Screen Compressed Plates for Monoamine Receptor Ligands

Last Updated on Thursday, 8 July 2010 01:21 Written by Editor Thursday, 8 July 2010 01:21

Scintillation Proximity Assay technology (SPA) provides a homogeneous assay format that is useful for receptor ligand binding assays. The homogeneous nature eliminates the separation steps necessary for filtration assays and enables optimization for automated high-throughput drug screening. Applying this technology to 384-well plate formats has allowed researchers to further increase assay throughput. However, not every assay adapts well to higher density plate formats, so another means of increasing assay throughput is required. In these cases we propose that screening with compound mixtures, or â€˜compressed plate screeningâ€™, is a useful alternative. Compressed plates are not new to the screening community, but the complexity of data analyzis and cumbersome follow-up investigations of primary hits have kept many researchers from using them^(1,2). This article addresses these limitations including the issues of false positives and the preservation of assay sensitivity. Additionally, compressed plate generation using compression algorithms and the process of deconvolution for the purpose for data analyzis are discussed. We propose that compressed plate screening is feasible when primary hit rates are low (<1%) and when screening at low compound concentrations (1Î¼M). Results indicated that more than 7-fold savings in time, money, and reagents after follow-up analyzis has been completed.

Compressed Plates

Testing mixtures of compounds in a well increases assay throughput, but a method for identifying active compounds from active mixtures is needed⁽³⁾. Using an algorithm to ‘compress’ 96-well microtiter plates in a ‘self-deconvoluting’ fashion, generated compressed plates in an 8:1 format. The 8:1 compressed plate contained 720 unique test compounds (18 or 20 compounds per well) and is prepared from eight 96- well plates containing 90 compounds each.

To reduce the imbalance in the number of compounds per well on the destination plate, the eight 96-well compound plates are reformatted into 9 x 10 matrices. These matrices are aligned to make two 18 x 20 matrices, or two â€˜source platesâ€™ (one source plate is shown in Figure 1).

Figure 1. One source plate (18 x 20 matrix).

Compounds in each 18 x 20 matrix are then combined to make row mixtures and column mixtures; each destination plate would have 36 row mixtures and 40 column mixtures containing 18 or 20 compounds per well. Row mixtures from source plates 1 and 2 (S1 and S2) were dispensed into the upper half of the destination plate (18 row mixtures each: S1R1â€“S1R18 and S2R1-S2R18). S1 and S2 column mixtures were dispensed into the bottom half of the destination plate (20 column mixtures each: S1C1-S1C20 and S2C1-S2C20). Wells H7-H12 are reserved for controls (Figure 2).

Figure 2. 96-well destination plate containing compound mixtures.

Each compound was present on the destination plate in two mixtures: one row and one column mixture. Both mixtures are otherwise unique, so that a positive assay result in two such wells identified one and only one compound. For example, if mixtures in wells A3 and E7 in the assay plate above were identified as active, the deconvoluting algorithm identifies the source plate or 18 x 20 matrix in which the compound resides. The algorithm also identified the original compound plate and the putatively active compound (identified by the intersection of the row 3 column 7 mixtures, Figure 3). Deconvolution of hits using the matrix layout was time consuming and error prone, so software was developed to automate the process.

Figure 3. Intersection of active column and row mixtures identifies compound.

An active row mixture and column mixture from a source plate was needed to identify an active compound; the intersection of row and column ‘uniquely’ identifies it. When more than one row and column mixture on a plate are active an individual compound has not been identified (Figure 4a). Assume compounds B11 and C10 were true actives. Compound C9 was falsely declared active because it was in column 3 (an active mixture because of compound B11) and in row 4 (an active mixture because of compound C10). A similar scenario exists for compound B12. The deconvolution program reported that all 4 mixtures (R3, R4, C3, and C4) were active in the assay, but could not decipher which combination of active mixtures constituted this activity. Therefore there was a configuration artifact which generated false positives. All four compounds had to be retested and only half (compounds in B11 and C10) were confirmed. This scenario becomes more complex as hit rates increased (Figure 4b). For effective screening, primary hit rates for 8:1 compressed plates should be <1% and the plate to plate hit rate variability should also be low.

Figure 4a. Configuration dilemma leading to false positives.

Figure 4b. Computer simulation deriving the % of false positives generated with increasing hit rate in compressed plates.

In addition to false positives generated with increasing hit rates, the presence of several compounds in a mixture also increased the likelihood of additive, synergistic, or antagonistic interactions^(2,3). Such interactions (in addition to pipetting errors) resulted in spurious hits, where a single row or column hit on a plate occurred without the corresponding column or row hit. In the absence of a correspondingly active mixture, this spuriously active well would not be flagged as a hit and would not need to be reconfirmed. The presence of several compounds in a mixture may reduce assay sensitivity, or the ability to identify an active compound within a mixture. Assay sensitivity was tested using 76 mixtures from an 8:1 compressed plate library using a receptor binding assay for serotonergic 5-HT_2C ligands (Figure 5). Hits were identified as compounds producing >50% inhibition of specific radioligand binding⁽⁴⁾. However, each of the 76 mixtures gave <50% inhibition in the assay and would not have been flagged as active in a screen. Mixtures were then spiked with 5-HT_2C ligands of varying affinity; MK212, mCPP, or metergoline⁽⁵⁾. In each of the inactive compound mixtures, these ligands were detectable, indicating that unknown mixtures do not adversely affect assay sensitivity. Additionally, the assay was able to distinguish between low, moderate, and high responses with compounds of varying affinity. Similar results were obtained using serotonergic 5-HT₇ and dopaminergic D₄ receptor binding assays (data not shown).

Figure 5. Measure of SPA 5-HT_2C receptor binding assay sensitivity.

Following compressed plate SPA assay development and validation, a screen was conducted for serotonergic 5-HT_2C ligands. Hits were identified as compounds producing >50% inhibition of specific radioligand binding. Fresh samples of these putative actives were obtained and tested individually. Confirmed active compounds were further evaluated for potency and receptor selectivity.

Results

Primary Screen

107,644 compounds were screened
88,744 compounds were screened in 8:1 compressed plates
18,900 compounds were screened in singleton plates (new compound acquisitions were not available in compressed plate format) Primary/Putative Hits
862 primary actives were identified (0.8% primary hit rate)
752 primary actives from compressed plates (0.8% compressed plate primary hit rate)
110 primary actives from singleton plates (0.6% singleton plate primary hit rate)

Confirmed Hits

369 compounds confirmed as actives (43% confirmation rate)
269 confirmed compressed plate hits (36% compressed plate confirmation rate)
100 confirmed singleton plate hits (91% singleton plate confirmation rate)

Final Hit Rate

Overall confirmed hit rate for the screen: 0.3%e
Overall compressed plate hit rate: 0.3%
Overall singleton plate hit rate: 0.5%

The 36% confirmation rate for primary actives in compressed plates seems remarkably low in comparison to the 91% confirmation rate for hits identified in singleton plates. Later screens for serotonergic 5-HT₇ ligands and dopaminergic D₄ ligands revealed similar hit rates for compressed and singleton plate sets.

The low compressed plate confirmation rates resulted from the complexity of the plate configuration and the deconvolution process. The computer simulation in Figure 4b illustrated the relationship between hit rates and false positives; the 0.8% primary hit rate in the 5-HT_2C screen generated the predicted number of false positives.

Although 862 putative actives had to be retested in order to confirm 369 active compounds, compressed plates still provided considerable savings in time and money. The primary screening and confirmation of hits from the 88,744 compounds tested in compressed plates required 164 assay plates. In singleton plate format, 986 plates would have been required to assay the same compounds. This reflects better than 7-fold savings in time, reagents, plates, and compounds for assays using 8:1 compressed plates.

With primary hit rates of <1%, follow-up and data analyzis were manageable. Compounds discovered in the screen can not yet be disclosed, the identification of several known commercial 5-HT_2C ligands in this assay (Table 1) further validates the feasibility of screening successfully with compressed plates.

Chlorpromazine	Amitriptyline
Chlorprothixene	Serotonin
Cinanserin	Clopenthixol
Cyproheptadine	Nortriptyline
Lisuride	Triflupromazine
MCPP	Melitracen
Methotrimeprazine
Methysergide	BP-400
Oxymetazoline	Doxepine
Trimeprazine	Prochlorperazine
Trimipramine	Phenyltoloxamine

Table 1. Known compounds identified in the 5-HT_2C SPA screen.

Conclusions

Testing compounds as mixtures in SPA receptor binding assays can dramatically reduce screening effort.

Additionally 8:1 compressed plate formats can further reduce screening effort by more than 7-fold when screening at low compound concentrations, when compound mixtures do not adversely affect assay sensitivity, and when hit rates are low. The deconvolution program identified false positives due to complexity of the compressed plate format, therefore all putative hits from mixtures had to be confirmed as singletons. It worked well when hit rates and plate to plate variability are low, such that the complexity of analyzis and follow-up were manageable. Although confirmation rates are likely to be much lower for compressed plate hits than those identified in singleton plates, the savings achieved via combination of SPA technology and compressed plate formats are substantial. Compressed plates can therefore provide an excellent format for increasing assay throughput when assays are not easily adaptable to higher density plate formats.

Source: las.perkinelmer.com

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Does Sun Exposure Cause Skin Cancer?

Last Updated on Wednesday, 5 May 2010 01:29 Written by Editor Wednesday, 5 May 2010 01:29

There are a lot of tales told about skin health. One of the most damaging is that sun exposure causes skin cancer. As youâ€™ll see in a moment, this is simply not true.
Melanoma is the form of skin cancer the media likes to refer to when they want to scare the dickens out of the public about the dangers of sun exposure. There are a number of reports of the fact that melanoma has been steadily increasing over the last 20 years. Most dermatologists will say this increase is due to the fact that more people are getting far too much sun exposure in their younger years.
A closer look at the matter, however, reveals a far different story. Skin cancer awareness programs have been effective at increasing the number of people undergoing full-body screening exams, and the result is a huge increase in the number of skin biopsies being performed. It seems that even with biopsies there is still considerable confusion and disagreement among pathologists when it comes to identifying melanoma. Itâ€™s apparently not a cut-and-dried diagnosis.
Looking at the same tissue, one pathologist will see a benign lesion while another will see it as melanoma. Thus, the dramatic increase in biopsies has led to more melanoma diagnoses, many of which are false, as a new study shows.
The study, conducted by doctors at Dartmouth Medical School, found that there has been a 250% increase in skin biopsies since 1986-which just happens to be roughly the same percentage increase in the number of people diagnosed with early-stage melanoma. These researchers became skeptical about the rise in melanoma after they noticed that over that time there hasnâ€™t been any increase in deaths from melanoma or any increase in the number of advanced cases of the disease. (BM] 05;331(7518):698)
Plain and simple, there has not been an actual increase in the overall incidence of melanoma. The apparent increase is due merely to improved detection because of the increased number of screening procedures and subsequent biopsies, which by the way, hasnâ€™t led to any increase in survival or cure rates.
Much like cancers of the prostate, breast, and lung, the more doctors look for cancer, the more likely they will find it and the number of false diagnoses will also increase.
If you or someone you know is diagnosed with melanoma, I would definitely suggest getting a second or possibly even a third opinion.
Obviously, excessive exposure that results in sunburn isnâ€™t a benefit at all. However, moderate amounts of sunlight, along with a varied diet containing natureâ€™s natural protective anti- oxidants, vitamins, and fatty acids (omega-3s) is actually beneficial and has been shown to help prevent many forms of cancer-including skin cancer.
Lifetime sun exposure was actually shown to result in a lower risk of developing melanoma. (I Invest Dermatol 03;120(6):1087-1093) Past studies have shown that individuals who utilize sun exposure reasonably have a lower incidence of colon and breast cancer, prostate cancer, multiple sclerosis, osteoporosis, hip and vertebra fractures, et cetera.
Over 20 years ago it was discovered that vitamin D has an â€œanti-proliferativeâ€ effect on cells. In other words, vitamin D can stop cells from multiplying out of control (i.e., from developing into cancer). The body has only two sources for vitamin D. The first is from oily foods (vitamin D is fat-soluble) such as oily fish, organ meats, and eggs. The second is from your own skin cells, which use the same â€œcancer-causingâ€ UV rays from the sun to convert a form of cholesterol into vitamin D.
Not surprisingly, those who consume more fish and omega- 3 foods have a reduced incidence of melanoma, while those consuming more of the omega-6 oils (the vegetable oils that are now so pervasive throughout our food supply) have increased rates of melanoma and other skin cancers.
A couple of other chemicals that your skin makes when it has adequate exposure to the UV rays of the sun. The function of these two vitamin D-related compounds, lumisterol and tachysterol, isnâ€™t yet fully understood. Itâ€™s possible that theyâ€™re associated with helping prevent blood sugar problems and obesity.
Avoiding sunlight puts you at a far greater health risk than exposing yourself moderately. Dr. William Grant, one of the top researchers on this subject, has studied the relationship between sunlight and health for years. Heâ€™s found that every year 47,000 individuals in this country die from 16 different types of cancer due to insufficient vitamin D, whereas 8,000 die of melanoma and another 2,000 die from other skin cancers.
Furthermore, pale skin, numerous moles, smoking, a diet high in fat and low in fruits and veg- etables, and frequent sunburns are all stronger predictors of later skin cancer than UV exposure. As with most things, moderation is the watchword. Enjoy your time in the sun every day and prepare your body with an adequate intake of the right fatty acids.

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Research yields new agent for some drug-resistant non-small cell lung cancers

Last Updated on Wednesday, 5 May 2010 01:14 Written by Editor Wednesday, 5 May 2010 01:14

BOSTON–The ability to make, test, and map the atomic structure of new anti-cancer agents has enabled a team of Dana-Farber Cancer Institute scientists to discover a compound capable of halting a common type of drug-resistant lung cancer.

“This type of drug discovery, in which an agent is developed for a specific gene or protein target, and then screened against cancer cells as well as in laboratory models, is rare in academic medicine,” says the study’s senior author Pasi A. JÃ¤nne, MD,PhD, of Dana-Farber and Brigham and Women’s Hospital (BWH). “This requires contributions from researchers in multiple disciplines and a coordinated approach to planning experiments and sharing results. That we accomplished this is evidence of the contribution academic medical centers can make to the quest for new cancer treatments.”

The study also illustrates how rapidly lung cancer research and treatment are advancing. It was less than five years ago that investigators at Dana-Farber and elsewhere traced some non-small cell lung cancers (NSCLCs) to mutations in the EGFR gene and discovered that Iressa and Tarceva slowed such tumors’ growth by targeting the abnormal EGFR protein. While the discovery has extended the lives of thousands of NSCLC patients around the world, EGFR blockers are only temporarily effective: after about eight months of treatment, the tumors begin to grow back. And because the drugs target normal EGFR protein as well as abnormal, many patients have severe side effects such as skin rashes and diarrhea.

All current EGFR inhibitors have a structural “backbone” known as a quinazoline core. They lodge in a notch on EGFR normally reserved for a molecule known as ATP, which delivers chemical energy to the cell. By blocking ATP from binding to EGFR, the inhibitors prevent EGFR from sending signals that are essential to keep the tumor cells growing.

Over time, however, the tumor cells develop additional abnormalities in EGFR, enabling them to recommence their growth, even in the presence of Iressa or Tarceva. The most common of these abnormalities — present in about 50 percent of patients with drug-resistant tumors ? is known as EGFR T790M.

Dana-Farber investigators hypothesized that current agents lose their potency because they don’t bind as tightly or fully to the EGFR T790M protein as they ideally should. To improve the fit, researchers led by chemical biologist Nathanael Gray, PhD, prepared a group of inhibitors with a different structural scaffold, known as a pyrimidine core, which, it was thought, would mesh more thoroughly. They lab-tested the agents in NSCLC cells with EGFR T90M and found several that were up to 100 times more potent than quinazolines in restricting cell growth. As an unexpected bonus, these compounds were nearly 100 times less powerful at slowing the growth of cells with normal EGFR, suggesting they would be less likely to produce side effects than current drugs. The agent which performed the best is the pyrimidine WZ4002.

“This work provides a possible therapeutic chapter to a longstanding record of validating EGFR as a drug target,” says Gray. “This has involved the identification of activating mutations in EGFR as a predictor of drug response, the discovery of multiple drug resistance mechanisms, and the elucidation of how these mutations work at an atomic level.”

In follow-up experiments, Dana-Farber and BWH’s Kwok-Kin Wong, MD, PhD, screened the pyrimidine agents in mice with Iressa- and Tarceva-resistant NSCLC tumors driven by EGFR T790M, and found them to be highly effective at impeding tumor growth. Dana-Farber’s Michael Eck, MD, PhD, conducted crystallography studies to determine the molecular structure of the pyrimidines, providing a better picture of why they are so potent and how they target EGFR T790M cells so precisely.

“Not only did we determine that the compound WZ4002 could slow tumor growth, we also demonstrated that it is possible to selectively target the drug-resistant mutant EGFR in tumors, with relatively less effect on the normal EGFR in healthy tissues,” says Wong.

Much work remains to determine if WZ4002 and its chemical cousins will be effective therapies, the authors caution, but the discovery demonstrates the power of screening specially designed compounds against cancers with certain genetic quirks.

“Obviously these are very early days with respect to the possible use of these compounds in patients ? we still have much to learn about their possible liabilities,” Eck remarks. “But I am optimistic that our approach is correct and that it will lead to an effective treatment for the thousands of non-small cell lung cancer patients worldwide who development resistance to Iressa and Tarceva every year.”

Other contributors to the study include lead author Wenjun Zhou, PhD, and co-first authors Dalia Ercan, Liang Chen, PhD, Cai-Hong Yun, PhD, as well as Danan Li, PhD, Marzia Capelletti, PhD, Alexis Cortot, MD, all of Dana-Farber; Lucian Chirieac, MD, and Robert Padera, MD, of Brigham and Women’s Hospital; and Roxana Iacob, PhD, and John Engen, PhD, of Northeastern University.

The study was supported by grants from the National Institutes of Health, the Cecily and Robert Harris Foundation, Uniting Against Lung Cancer, the Flight Attendant Medical Research Institute, the Hazel and Samuel Bellin research fund, and the Damon Runyon Foundation.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

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Bioluminescence imaging allows real-time monitoring of cancer spreading through the body

Last Updated on Wednesday, 5 May 2010 01:13 Written by Editor Wednesday, 5 May 2010 01:13

(Nanowerk News) Scientists from A*STAR in Singapore and the USA have developed a fast bioluminescence imaging technique that may greatly assist in the search for drugs that target mobileâ€”or metastaticâ€”cancer cells (“A screening platform for glioma growth and invasion using bioluminescence imaging Laboratory investigation”).
Chemotherapy treatments for this type of cancer using â€˜anti-migratoryâ€™ drugs are important because some of the most mobile cells that cause metastasis can resist conventional cancer drugs. This is a problem because patients tend to be at greater risk of developing metastases over the extended survival periods associated with modern cancer therapies. Using zebrafish as a model organism, researchers could spot as few as eight cells undergoing metastasis from glioblastoma multiforme (GBM)â€”the most common and aggressive type of brain tumor.

Embryos of Zebrafish could provide important insights into the spread of cancer throughout the body.
The team, including Beng-Ti Ang from A*STAR’s Singapore Institute for Clinical Sciences and co-workers at the University of Singapore and the Methodist Hospital, Cornell University, USA, used a method called gene transfection to develop GBM cells that express a gene from fireflies, causing them to emit light in a process known as bioluminescence. They assessed the â€˜invasivenessâ€™ of the cells by measuring how quickly they moved through a three-dimensional matrix, and found that the most invasive cells express a gene that makes them more mobile. The same gene has also been correlated previously with reduced patient survival.
The researchers then injected the GBM cells into zebrafish embryos, and observed tumors in the embryos a few days later. By placing the embryos under a charge-coupled device camera, they were able to watch the bioluminescent tumor cells growing and moving around the body, invading other organs.
â€œThe advantages of the zebrafish are that it is transparent under microscopy imaging, has a fast development cycle (major features are seen within 24 hours after birth), and it is a vertebrate animal,â€ explains Stephen Wong of the Methodist Hospital. Furthermore, the zebrafish tumors have genomes and development processes very similar to human cancers.
This new bioluminescence screening platform represents a unique real-time method for observing small numbers of cancer cells in a live animal. It is cheaper, easier and far more sensitive than existing imaging methods such as positron emission or computed tomography scanning, or magnetic resonance or fluorescent imaging. Furthermore, the discovery of a genetic subset of highly invasive GBM cells could help greatly in the development of drugs that target tumor-initiating cells.
The team plans to use the platform to screen anti-migration and invasion candidate compounds for GBM treatment and extend the platform for drug screening in other invasive tumors and for drug combination studies.

Source: A*STAR/nanowerk.com

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New Agent for Some Drug-Resistant Non-Small Cell Lung Cancers

Last Updated on Wednesday, 5 May 2010 01:12 Written by Editor Wednesday, 5 May 2010 01:12

ScienceDaily (Dec. 28, 2009) â€” The ability to make, test, and map the atomic structure of new anti-cancer agents has enabled a team of Dana-Farber Cancer Institute scientists to discover a compound capable of halting a common type of drug-resistant lung cancer.

In a study to be published in the December 24/31 issue of the journal Nature, the researchers report that non-small cell lung cancers that had become invulnerable to the drugs IressaÃ¢ and TarcevaÃ¢ were stymied by a compound designed and formulated in a Dana-Farber lab. The compound, whose basic chemical framework is different from that of other cancer drugs, acts against a protein — known as an epidermal growth factor receptor (EGFR) kinase — that carries a specific structural defect.”This type of drug discovery, in which an agent is developed for a specific gene or protein target, and then screened against cancer cells as well as in laboratory models, is rare in academic medicine,” says the study’s senior author Pasi A. JÃ¤nne, MD,PhD, of Dana-Farber and Brigham and Women’s Hospital (BWH). “This requires contributions from researchers in multiple disciplines and a coordinated approach to planning experiments and sharing results. That we accomplished this is evidence of the contribution academic medical centers can make to the quest for new cancer treatments.”

“Obviously these are very early days with respect to the possible use of these compounds in patients — we still have much to learn about their possible liabilities,” Eck remarks. “But I am optimistic that our approach is correct and that it will lead to an effective treatment for the thousands of non-small cell lung cancer patients worldwide who development resistance to Iressa and Tarceva every year.”

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Ambit Biosciences and Astellas Enter Strategic Partnership to Research, Develop and Commercialize FLT3 Kinase Inhibitors in Multiple Indications

Last Updated on Wednesday, 5 May 2010 11:46 Written by Editor Wednesday, 5 May 2010 11:46

Ambit to Receive a US$40 Million Upfront Cash Payment; Up to US$350 Million in Pre-Commercialization Milestones, Double-Digit Royalties with Option to Co-promote and Share Profits in U.S.

SAN DIEGO and TOKYO, December 18 – Ambit Biosciences Corporation and Astellas Pharma Inc. today announced
that they have entered into a worldwide agreement to jointly develop and
commercialize FLT3 kinase inhibitors in oncology and non-oncology
indications. This partnership includes AC220, Ambit’s lead clinical-stage
investigational drug that entered into a Phase 2 clinical trial earlier this
month in relapsed/refractory acute myeloid leukemia (AML), and other
undisclosed FLT3 kinase inhibitors. AC220 is a novel, orally available,
potent and highly selective small molecule that was specifically designed as
a second generation FMS-like tyrosine kinase-3 (FLT3) inhibitor using Ambit’s
proprietary drug discovery engine, KINOMEscan(TM).

The companies will collaborate to develop AC220 for AML and other
indications. The parties will also collaborate on a research and development
program for a series of novel FLT3 inhibitors for a variety of oncology and
non-oncology indications. The companies will share equally in the
responsibilities and expenses for the development of AC220 and any additional
products in the U.S. and Europe, while Astellas will have sole responsibility
to fund development in all other territories. Under the terms of the
agreement, Ambit will receive an up-front cash payment of US$40 million and
will be eligible to receive pre-commercialization payments of up to US$350
million.

Astellas will have sole responsibility for funding and implementing the
commercialization of all products, and Ambit will be entitled to
post-approval milestone payments upon the achievement of certain sales
thresholds, as well as tiered double-digit royalties on net sales. In the
U.S., Ambit will also have the option to co-promote AC220 and other products
under a profit sharing arrangement where Astellas and Ambit share equally in
profits and losses generated from U.S. sales.

“We are pleased to have entered into a great partnership with Ambit,”
stated Masafumi Nogimori, president and chief executive officer of Astellas.
“We believe that AC220, as the most selective and advanced FLT3 kinase
inhibitor, has the potential to provide a new treatment option for AML where
high unmet medical needs exist. Astellas is strongly committed to focus on
oncology and this partnership is a significant milestone to establish our
franchise in oncology.”

“With their strategic commitment to the development and commercialization
of innovative oncology products, Astellas is an ideal partner for Ambit,”
said Scott Salka, Chief Executive Officer of Ambit Biosciences. “This
collaboration establishes a comprehensive and global leadership position in
the discovery and development of FLT3 kinase inhibitors, and we look forward
to working closely with Astellas to explore the clinical utility of AC220 in
AML and other indications.”

About AC220

AC220, Ambit’s lead product candidate, is being developed in
collaboration with Astellas Pharma Inc. and is a novel, potent, highly
selective, orally bioavailable second-generation FLT3 inhibitor. AC220 is
currently under evaluation in a Phase 2 clinical trial designed to support
potential registration of AC220 as monotherapy treatment in adult and elderly
patients with relapsed/refractory AML that have the internal tandem
duplication (ITD) mutation in the FLT3 kinase. AML is one of the most common
types of blood cancers in adults, and the FLT3 kinase is mutated and
constitutively activated in 25-40 percent of such patients. FLT3 ITD
mutations predict poor prognosis and decreased response to existing
treatments, including chemotherapy and hematopoietic stem cell transplant.
Ambit leveraged KINOMEscan(TM), the company’s proprietary, high-throughput
method for screening small molecule compounds against a large number of human
kinases, to advance AC220 from initial chemistry to clinical candidate
selection for IND-enabling studies in only 18 months.

About Acute Myeloid Leukemia (AML)

Acute myeloid leukemia is a form of blood cancer. According to the
American Cancer Society, approximately 13,000 new cases of AML will be
diagnosed in the United States in 2008. The median age of a patient with AML
is about 67 years. Standard treatment for patients 60 years or older with AML
includes systemic combination chemotherapy. The median survival for patients
receiving induction chemotherapy, which is associated with high mortality, is
6-11 months, with shorter survival for patients over the age of 60 years. The
five-year survival rate for AML is less than 15 percent. According to a
report from Decision Resources, the U.S. AML market is expected to more than
double by 2015.

About Ambit Biosciences

Ambit Biosciences is a privately-held biopharmaceutical company engaged
in the discovery and development of small molecule kinase inhibitors for the
treatment of cancer, inflammatory disease, and other indications. Ambit
employs a novel and proprietary kinase profiling technology, KINOMEscan(TM),
to screen compounds against 442 human kinases.

Ambit’s lead compound, AC220, is in clinical development for the
treatment of AML and other indications. Ambit has initiated a Phase 2 pivotal
trial in patients with relapsed or refractory AML and plans to commence
several other clinical studies with AC220 in 2010. Ambit’s clinical pipeline
also includes AC480, an oral pan-HER inhibitor that was in-licensed from BMS.
Ambit is conducting Phase 2 studies with AC480 in patients with solid tumor
cancers. Additionally, Ambit has an advancing pool of preclinical candidates
targeting BRAF (in collaboration with Cephalon), JAK2, Aurora, and CSF1R.
Through its KINOMEscan Division, Ambit markets its technology as a profiling
service. For more information, visit www.ambitbio.com.

About Astellas

Astellas Pharma Inc., located in Tokyo, Japan, is a pharmaceutical
company dedicated to improving the health of people around the world through
the provision of innovative and reliable pharmaceuticals. Astellas has
approximately 15,000 employees worldwide. The organization is committed to
becoming a global category leader in urology, immunology & infectious
diseases, neuroscience, DM complications & metabolic diseases and oncology.
For more information on Astellas Pharma Inc., please visit our website at
www.astellas.com/en.

Contact:
--------
Ambit Biosciences:                       Astellas Pharma:
------------------                       ----------------
M. Scott Salka                           Corporate Communications
+1-858-334-2101                          +81-(0)3-3244-3201
www.astellas.com/en/
Christopher Morl (business development)
+1-858-334-2134

Scott Lerman (media)
The Ruth Group
+1-646-536-7013
slerman@theruthgroup.com

Sara Pellegrino (investors)
The Ruth Group
+1-646-536-7002
spellegrino@theruthgroup.com

Source: blog.taragana.com

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We’re winning the war on cancer

Last Updated on Wednesday, 5 May 2010 11:38 Written by Editor Wednesday, 5 May 2010 11:38

What does yesterday’s exciting news of the complete DNA sequencing of two different cancers mean? It is a fantastic feat that promises great improvements in our ability to cure cancer by 2020, but it comes with a hefty price tag.

The numbers are stark. One in three of us will get cancer, and 1.5 million Britons alive today have either had it or have been treated for it. Globally, 10 million people will get cancer this year and this will reach 20 million by 2020.

Cancer is predominantly a disease of people over 60, so paradoxically, this is good news. The growing number of cancers is because there are more old people â€“ and so fewer deaths among the young.

The most promising advances on the horizon come from our rapidly increasing understanding of the cog molecules that make cancer cells tick. That’s what yesterday’s excitement was about. Imagine that your car breaks down. The difference between you and the roadside repair man is that he knows what goes on under the bonnet, while you can’t even open it.

So we can now compare the exact DNA sequences of five different cancers from real people. Painstaking analysis of these and other data will allow us to work out what went wrong. Eventually this will have a considerable impact on prevention, screening, diagnosis and treatment, and will herald a new golden age of drug discovery.

In the past 20 years, a huge amount of fine detail of the basic biological processes that become disturbed in cancer has been amassed, and the pace is quickening.

We now know the key elements of how signals for growth bind to cells and how messages can get corrupted, leading to uncontrolled growth or failure to die. These are fertile areas to look for rationally based, anti-cancer drugs. This approach has already led to a record number of new compounds in trials, currently estimated to be about 700.

Over the next few years, there will be a marked shift in the type of agents used in the systemic treatment of cancer. They will be precisely targeted to the defined abnormalities found in individual patients.

Because we know the precise targets of these new agents, there will be a revolution in cancer therapy. Instead of defining drugs for different types of cancer empirically and relatively ineffectively, we will identify a series of molecular lesions in tumour samples. Future patients will receive drugs that target these lesions directly.

The human genome project provides a vast repository of comparative information about normal and malignant cells. The new therapies will be more selective, less toxic and be given for prolonged periods of time, in some cases for the rest of the patient’s life. This will lead to a radical overhaul of how we provide cancer care.

Personalised medicine, based on a set of novel molecular diagnostics, will allow us to give the right medicine to the right patient at the right time. Small black boxes into which patients put a blood sample will guide treatment and monitor its effectiveness. Tiny, implantable chips sending radio signals to a home computer will permit continuous monitoring.

Individual cancer risk assessment will lead to tailored prevention messages and a specific screening programme to pick up early cancer, with far-reaching public health consequences. Preventive drugs will be developed to reduce the risk of further genetic deterioration.

But in this bright future, the funding of cancer care will become a significant problem. Already we have seen inequity in access to the drugs Sutent for kidney cancer and Avastin for colon cancer.

For the moment, these drugs are only palliative, adding just a few months to life. But the emerging compounds are likely to be far more successful, and their long-term administration considerably more expensive.

As consumerism increases in medicine, patients will become more informed and assertive, seeking out new therapies and bypassing traditional referral pathways.

New financial structures will arise, with the pharmaceutical, insurance and health care sectors combining to enable future patients to choose the levels of care they wish to pay for, through insurance or directly.

By 2025, chemotherapy is likely to replace other treatments for many cancers. Cancer will become a chronic, controllable illness, like diabetes today. People living with cancer will receive care in attractive, hotel-like environments rather than hospitals, run by competing private-sector providers. Global franchises will use the web to disseminate treatment plans and control their quality.

This transition will bring new ethical dilemmas. The future will be decided by the interaction of four complex factors: technological success, society’s willingness to pay, future health care delivery systems and the financial mechanisms that underpin them.

Cure will still be sought, but it will not be the only satisfactory outcome. Patients will be closely monitored after treatment, but the fear that cancer will definitely kill, still prevalent today, will be replaced by an acceptance that many forms of cancer are a consequence of old age.

Fast-tracking the diagnosis makes good sense. Cancer masquerades as many other less serious illnesses, so even the most experienced GP can’t pick out who actually has the disease. The NHS is often a slow and cumbersome system in which to get the necessary tests. Many cancers have already spread by the time they are eventually diagnosed.

We are still the poor man of Europe in comparative studies of access to diagnostics, despite Gordon Brown’s recent announcement that nobody will have to wait more than seven days for tests. Unfortunately this is aspirational propaganda.

Predicting the future is fraught with difficulties. Who could have imagined in the 1980s the impact of mobile phones, the internet and low-cost airlines on global communication? Medicine will be overtaken by similarly unexpected step changes in innovation.

For these reasons, economic analysis of the impact of developments in cancer care is difficult. The greatest benefit will be achieved simply by assuring that the best care possible is on offer to the most patients. This would be irrespective of their socio-economic circumstances and of any scientific developments.

But this dream is simply unrealistic. Technologies are developing fast, particularly in imaging and the exploitation of the human genome. Well-informed patients, with adequate funds, will ensure that they have rapid access to the newest and the best â€“ anywhere in the world.

More patients will benefit from better diagnosis and newer treatments, with greater emphasis on quality of life. But innovation will inevitably bring more inequality to health. The outcome of the same quality of care differs today between socio-economic groups and will continue to do so.

It is the job of governments to ensure health equity for all their constituents. Living long and dying fast will become the mantra of this century. Profound challenges lie ahead.

Professor Karol Sikora is medical director of CancerPartnersUK and Dean of the University of Buckingham Medical School.

source: telegraph.co.uk

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Anti-cancer compound wins scientist Biota Award

Last Updated on Monday, 11 January 2010 06:14 Written by Editor Monday, 11 January 2010 06:14

Walter and Eliza Hall Institute scientist Dr Guillaume Lessene has won this year’s Biota Award for Medicinal Chemistry, awarded by the Royal Australian Chemical Institute.

Dr Lessene, who runs a laboratory in the institute’s Structural Biology Division, won the award for his role in the discovery of several compounds that interact with a protein that has been implicated in the poor response of many cancers to anti-cancer treatments.

The protein is a member of the Bcl-2 family of proteins. This protein family has a role in tumour development, anti-cancer-drug resistance and cancer spread. Dr Lessene’s drug target, in particular, is thought to be involved in the drug resistance of many tumours.

The Biota Award is presented annually to the chemist judged to be responsible for the best drug design and development paper published, patent taken out, or commercial-in-confidence report concerning small molecules as potential therapeutic agents.

Together with eight co-inventors Dr Lessene has made a patent application that describes how his compounds could be used to restore the cell death process that is important in combating the growth of cancers.

Since 2001 Dr Lessene has focused his research on developing small molecules that inhibit the Bcl-2 family of proteins.

“It is expected that drugs targeting Bcl-2-like proteins will have a major impact in cancer treatment,” he said.

Usually, when a cell’s DNA is damaged the cell tries to repair itself and, if it can’t, undergoes a process of programmed cell death.

Cancer develops when, despite cells having DNA damage, they don’t die but continue to divide, leading to tumour formation. This happens when the signal that tells the cell to die is inhibited by Bcl-2 proteins, which allows the cell to keep dividing.

Through high throughput screening, medicinal chemistry, and structure-guided drug design, Dr Lessene and the institute’s drug discovery team have been identifying and refining compounds that inhibit the Bcl-2 proteins.

“From a drug discovery point of view the Bcl-2 proteins are challenging targets because of the size and shape of their binding sites,” Dr Lessene said. “Our successful work therefore represents a considerable achievement, particularly in the field of protein-protein interactions.”

The research leading to the discovery of these compounds is the basis of a collaboration and licensing agreement between the Walter and Eliza Hall Institute, Genentech Inc and Abbott, the leader in Bcl-2 inhibitor development.

Dr Lessene is the second person from the Walter and Eliza Hall Institute to win the Biota Award. Dr Jonathan Baell, also from the Structural Biology Division, received the award in 2004.

Source: Walter and Eliza Hall Institute

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AACR-NCI-EORTC conference highlights major expansion in cancer drug pipeline

Last Updated on Monday, 11 January 2010 03:24 Written by Editor Monday, 11 January 2010 03:24

The last decade has seen a major expansion in the cancer drug pipeline and studies are continually underway to advance the arsenal of drugs and create more effective treatments and targeted therapies for patients.

To highlight results of more recent research, the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference will host a press briefing on “Drugs in the Pipeline.” Sara A. Courtneidge, Ph.D., D.Sc., professor and director of the Tumor Microenvironment Program, and director of academic affairs at the Burnham Institute for Medical Research, will moderate this press briefing.

“Conferences such as the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference play a very important role in advancing translational cancer research. Here, one can learn about the newest breakthroughs across the continuum of cancer research,” said Courtneidge.

Breakthroughs to date have been made in the development of anti-angiogenesis inhibitors that target the tumor vasculature and of modulators of gene expression and protein stability, according to Courtneidge. Many more agents have been added to the pipeline of cancer drugs, including inhibitors that target the BCR-ABL fusion protein and other kinases. Cytotoxic agents remain a mainstay of cancer therapy, and inhibitors of DNA repair and cancer stem cells show great promise.

The press briefing will take place on Monday, Nov. 16, 2009, from 1:00 p.m. to 2:00 p.m. ET, in Room 202 of the Hynes Convention Center in Boston, Mass.

Reporters who cannot attend in person may call using the following information:

U.S./Canada: (888) 282-7404
International: (706) 679-5207
Access Code: 36170264
Topic: AACR

Leading researchers will present new and exciting data on the role of hsp70 as a novel therapy for breast cancer; various drug compounds that kill leukemia stem cells and yet spare normal stem cells; tolerability results of cediranib for use in children with recurrent or refractory solid tumors; and sensitivity study results of olaparib for colorectal cancer cells containing a specific DNA repair defect.

“This research spans studies on the genetic makeup of cancer cells, validation studies on the roles of key signaling proteins and pathways, the development of novel agents, and the testing of those agents in a variety of pre-clinical and clinical settings,” Courtneidge added.

The following abstracts will be presented during this press briefing:

# B21. Targeting autophagy induced by pan-HDAC inhibitor panobinostat and promoted by acetylated hsp70: A novel therapy for breast cancer

Targeting heat shock response protein with panobinostat, combined with an autophagy inhibitor, is an effective treatment strategy against growing stress cells in breast cancer.

“Clearly this points to a very new approach of targeting heat shock response in combination treatment,” said Kapil Bhalla, M.D., director of the Medical College of Georgia Cancer Center, professor of medicine in the Department of Medicine, Division of Hematology-Oncology at the Medical College of Georgia, and vice president for cancer research at the Medical College of Georgia.

Panobinostat is a potent histone deacetylase (HDAC) inhibitor that has been shown to induce cell death of tumor cell lines, but not the normal cells. In breast cancer cells where programmed cell death is inhibited, pan-HDAC inhibitor treatment induces autophagy, which allows the breast cancer cells to escape elimination.

Bhalla and colleagues evaluated the stress phenotype of breast cancer cells in the mammary fat pad of mice when mediated by two heat shock proteins â€” hsp90 and hsp70, which help to promote cancer survival. The researchers wanted to determine how these inhibitors that deacetylate proteins and histones affect the cell’s function.

“Basically we forced the cancer cell to have autophagy and then pulled the rug from under it by having an autophagy inhibitor take that away,” said Bhalla.

Treatment with panobinostat induced acetylation of amino acid lysine in the hsp70 protein. With growing tumor size they found an increase in hsp70, heat shock response and autophagy.

“Panobinostat accentuates stress, causes autophagy, and sets up the cell to be eliminated by autophagy inhibitors,” Bhalla said.

Panobinostat is not FDA approved for use in breast cancer.
# A51. Identification of compounds targeting human leukemia stem cells

Researchers at the University of Michigan, Ann Arbor, and the University Health Network, Toronto, have found a new paradigm for screening against leukemia stem cells that can target them and spare blood-forming stem cells at the same time.

The researchers identified small molecules, potentially novel or those currently known, that kill leukemia stem cells, but not normal blood-forming hematopoietic stem cells, which are multipotent stem cells that give rise to all blood types. Three of the 10 compounds they studied targeted leukemia stem cells: ciclopirox olamine, etoposide and kinetin riboside.

“Treatment with these compounds, at the appropriate doses, would kill the leukemia cells and potentially minimize blood system side effects, such as anemia,” said Sean McDermott, Ph.D., research investigator in the Department of Internal Medicine, Hematology-Oncology at the University of Michigan Medical School.

In total, the researchers screened a collection of 4,000 small molecules using two novel leukemia cell lines that have properties of leukemia stem cells. Compounds that killed these leukemia cells were further tested on normal hematopoietic stem cells to remove toxic compounds.

“Overall, to find three compounds that target the leukemia stem cell, all with vastly different mechanisms, is extremely surprising and bodes well for future drug discovery efforts,” said McDermott.

Cells from 51 patients with acute myeloid leukemia (AML) and 12 patients with chronic myelogenuous leukemia (CML) were screened with one of the drugs, etoposide. The researchers were surprised by the etoposide results, which showed that the drug may target the leukemia stem cell in 30 percent of patients with AML and 67 percent of those with CML. These patients might benefit from treatment with this chemotherapeutic drug.

“Screening of larger libraries hopefully will identify even more agents for the cancer pipeline,” he added.

Follow-up studies are currently planned for ciclopirox olamine and it would be beneficial in evaluating low-dose etoposide as a single agent. Kinetin riboside may be tested in a clinical setting in the future, according to McDermott.

# A5. Phase I trial and pharmacokinetic study of cediranib in children with recurrent or refractory solid tumors

Results of a new study show that cediranib can be administered safely to children and adolescents with cancer, and that the side effects are tolerable. Preliminary evidence further showed that the drug may have activity in childhood sarcomas.

“There are a number of antiangiogenic agents, like cediranib, in development for adult cancers,” said researcher Elizabeth Fox, M.D., M.S.C.R., staff clinician in the Pediatric Oncology Branch at the National Cancer Institute. “Encouraging results seen in this trial provide a rationale for future clinical trials of cediranib and other antiangiogenic agents in childhood cancer.”

Cediranib is an oral drug that inhibits vascular endothelial growth factor receptor. The recommended dose in adults is 20 mg to 30 mg administered daily every day for 28 days.

Fox and colleagues tested the toxicity and tolerance of this drug when given in 28-day cycles to patients 2 to 19 years old with malignant solid tumors to determine the appropriate dose of cediranib for this age group. Patients who participated in this phase I study had not responded to or recurred after conventional therapy.

Among the 13 patients enrolled, once daily dosing of 12 mg/m2 of cediranib was tolerable. Thus far, three patients have experienced partial shrinkage of their tumor while receiving the antiangiogenic agent. Side effects in children were similar to those seen in adults on cediranib: dose-limiting toxicities were diarrhea, nausea, vomiting, lethargy and high blood pressure.

“This outcome is encouraging and provides evidence that cediranib should be further studied in future clinical trials in young patients with these and other sarcomas to determine the activity of this new agent,” Fox said. “Hopefully, newer classes of anti-cancer drugs currently being developed will have fewer acute and long-term side effects than the chemotherapy that we currently use to treat childhood cancers.”

The researchers are currently evaluating the effects with 17 mg/m2 of cediranib and proposed to the Children’s Oncology Group that a phase II study be conducted in selected childhood solid tumors.

# A114. Preclinical evaluation of the PARP inhibitor olaparib in homologous recombination deficient (HRD) MRE11 mutant microsatellite instable (MSI) colorectal cancer

The investigational cancer therapy olaparib demonstrated activity against colorectal cancer cells, which suggests that microsatellite instable colorectal cancer represents a potential patient population that could benefit from treatment with this agent.

Researchers have already evaluated the use of the oral poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib and its antitumor activity pre-clinically and in patients with breast and ovarian cancer that contain a specific DNA repair defect in the form of BRCA1 and BRCA2 mutations. These gene mutations are associated with hereditary breast and ovarian cancer and play a major role in the repair of DNA by the homologous recombination repair pathway. PARPs also play a major role in DNA repair, by working in an alternative pathway.

Olaparib exploits the “Achilles’ heel” of homologous recombination deficient cancers by blocking another DNA repair pathway in these already compromised cancer cells, therefore leading to an overload of DNA damage and resulting in tumor cell death. The activity of one such homologous recombination gene, MRE11, is lost as a consequence of microsatellite instability in colorectal cancer cells.

“DNA damage is occurring all the time in our cells and a number of mechanisms have evolved to repair this damage that include the PARP and the homologous recombination repair pathways,” said Mark O’Connor, Ph.D., chief scientist at KuDOS Pharmaceuticals Ltd., United Kingdom.

The aim of this study was to determine if microsatellite instability and MRE11 status correlated with sensitivity to olaparib. Olaparib is an oral anti-cancer drug in early development for the treatment of certain types of breast and ovarian cancer.

The researchers found the majority of colorectal cancer cell lines sensitive to olaparib correlated with microsatellite instability status and had MRE11 mutations. Furthermore, all olaparib-sensitive colorectal cancer cell lines were homologous recombination deficient.

“These results reinforce the idea that PARP inhibition might have broader clinical utility than in BRCA-deficient tumors alone,” said O’Connor. “They support the idea of using targeted cancer therapies in defined molecular genetic backgrounds that exploit specific DNA repair deficiencies in the cancer to be treated.”

http://www.eortc.be/

Source: news-medical.net

Posted under Cancer Research, Drug Development, Oncology Research, Press Releases | No Comments

Tapeworm Drug May Hold Promise For Colon Cancer, Future Research

Last Updated on Tuesday, 15 December 2009 03:22 Written by Editor Tuesday, 15 December 2009 03:22

The findings about this compound, published in the Nov. 3 issue of Biochemistry journal, might prove valuable to patients and clinicians, who may benefit if there is a demonstrated boost to chemotherapy. Researchers also can use the compound to manipulate the receptor to learn more about a common cell replenishing pathway, called the Wnt pathway, which requires the receptor for normal activities and can go wrong in cancer cases.

The researchers had a choice: to screen libraries of several hundred thousand biochemical compounds or to use a library of about 1,200 FDA approved or biologically active compounds.

â€œWe decided to take the less expensive route of screening FDA approved drugs, and fortunately, we found 26 compounds that seemed to meet our goal, but only one that truly worked with the Frizzled receptor,â€said Wei Chen, Ph.D., Assistant Professor of the Department of Medicine at Duke. â€œThe goal was to drive the Frizzled 1 receptor from the outer membrane to the inside of the cell,â€ which effectively inactivated the receptor.

The effective compound, niclosamide, is currently approved for use against tapeworm infection. But some colon cancer patients, for example, have a Wnt pathway that is overactivated and may benefit from the â€œquietingâ€ effects of niclosamide, which blocks the receptor in the Wnt pathway.

â€œThe paper provides a rationale for clinicians to investigate using niclosamide for a new purpose,â€ Dr. Chen said. â€œBased on our findings, one oncologist at Duke is writing protocols for a phase 1 (safety) clinical trial to treat colon cancer patients with the intention of bringing our laboratory findings to the patientâ€™s bedside.â€

Chen says he is proud of the work, which is â€œtruly translational science.â€

â€œI am a basic scientist working with cell receptors, we have a medicinal chemist in our laboratory and one of our collaborators is Dr. H. Kim Lyerly, a professor of surgery, who is a researcher in gene- and immune-based therapies for cancer, as well as director of the Duke Comprehensive Cancer Center,â€ said Chen. â€œThis type of diverse collaboration lets me shepherd a finding more rapidly from the laboratory to the clinic.â€

Provided by Duke University Medical Center

physorg.com

Posted under Cancer Research, Discoveries, Innovations and Patents, Drug Development, Drug-Like Compounds, Oncology Research, Press Releases | No Comments

Scientists hope mouse research leads to new anti-cancer therapies

Last Updated on Wednesday, 2 December 2009 12:28 Written by Editor Wednesday, 2 December 2009 12:28

Can an experiment with rodents lead to the end of breast cancer as we know it?

Recent collaborative work between Cambridge, Mass., research institutes has discovered a method of screening for chemicals that selectively kill breast cancer stem cells in culture and in mice, a breakthrough that may directly or indirectly lead to new anti-cancer therapies.

â€œOne of the major difficulties with developing good anti-cancer drugs is that the anti-cancer drugs donâ€™t cure the tumors, and part of the reason they donâ€™t cure the tumors is that theyâ€™re not very effective in specifically attacking and eliminating the cancer stem cells,â€ said Dr. Robert Weinberg, founding member of the Cambridge-based Whitehead Institute and a biology professor at MIT. â€œWeâ€™re trying to develop techniques to understand what creates cancer stem cells and how they are perpetuated.â€

A theory prevalent amongst many researchers suggests that the aggressive subset of cancer cells — called cancer stem cells — drives tumor growth and causes tumors to regenerate after chemotherapy has killed 99 percent of their cells.

Isolating true-to-form cancer stem cells proved to be a challenge until recently, when researchers at Weinbergâ€™s lab at the Whitehead Institute discovered a method to manipulate these cells.

The discovery allowed a team of scientists led by Dr. Piyush Gupta of the Cambridge-based Broad Institute to derive cell lines from human breast epithelial cells and use them to screen 16,000 chemicals in culture dishes. The scientists found that 32 of these chemicals specifically target cancer stem cells and kill them.

Guptaâ€™s team then tested the chemical compounds in mice, and narrowed the results down to one chemical, salinomycin, that appeared to shrink tumor growth. The study was published in an August issue of the journal Cell.

â€œOurs was really the first step in a long process.â€ Gupta said. â€œWe have one compound now, and it is not clear whether this one compound is ideal in terms of its activity and also in terms of its toxicity.â€

The discovery of the potent chemical does not necessarily mean that it will have any improvement over current cancer treatment. Guptaâ€™s team has started the extensive follow-up testing that is necessary to determine in which stage eliminating cancer stem cells would be most beneficial to patients, and whether the compound is suitable for humans at all.

â€œThings sometimes appear very promising in pre-clinical studies but then in patients they may for whatever reason not work as well,â€ Gupta said. â€œAll we can do is try to design the best possible preclinical studies in the hope that it will work in the patients. We really want to understand how the compounds work in animals before we even think about putting them in people.â€

Still, the new screening method is a promising development in the field of anti-cancer treatment. Gupta said he expects some cancer stem cell-targeting therapies to make into human trials within three to five years.

â€œFor a while it seemed like these cancer stem cells were exciting, but there was very little known about them,â€ Gupta said. â€œNow I think that weâ€™re finally at the stage where we can really start to understand whatâ€™s going on inside these cells.â€

Wicked Local Cambridge

Source: tauntongazette.com

Posted under Cancer Research, Compound Screening, Discoveries, Innovations and Patents, Oncology Research, Press Releases | No Comments

PharmaGap Reports That GAP-107B8 Showed Strong and Consistent Anti-Cancer Activity in a Wide Range of Cancers in NCI Test

Last Updated on Wednesday, 2 December 2009 12:26 Written by Editor Wednesday, 2 December 2009 12:26

OTTAWA, ONTARIO, Oct 27, 2009 (MARKETWIRE via COMTEX) —-PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF) (“PharmaGap” or “the Company”) is pleased to announce highly positive results from the United States National Cancer Institute (“NCI”) 5-dose in vitro anti-cancer screen of PharmaGap drug GAP-107B8. These results confirm and extend results announced in August from the single-dose study and provide definitive independent validation of GAP-107B8 as an active pharmaceutical ingredient against a wide range of cancers.

GAP-107B8 is a novel peptide protein kinase inhibitor that was designed to specifically target molecular signaling pathways in cancer cells. Targeted therapies are designed to target cancer cells while sparing surrounding normal, healthy, cells, thus causing less toxic effects than many standard chemotherapeutic agents currently in use.

Within a dose concentration range of 10 to 100 micromolar (u M), GAP-107B8 caused 100% growth inhibition (measured against cancer cell growth in untreated groups) in 51 of 56 cancer cell lines and caused at least 50% cancer cell death (measured against the number of cancer cells at the beginning of the test period) in 29 of 56 cancer cell lines.

The standard NCI test methodology generates three values that are used to measure the drug compound’s activity against the cancer cell-line panel. These are: the GI50, the dose that causes an average 50% growth inhibition in the cell lines; the TGI, the dose that causes an average 100% growth inhibition in the cell lines; and the LC50, the dose that causes an average 50% cell death in the cell lines. For GAP-107B8, the GI50 was determined to be 23 u M, the TGI was 51 u M, and the LC50 was 89 u M. These data provide a very clear range of focus for all future studies.

These results provided a large amount of data, from the NCI testing which will be used by the Company to select specific cancer types and to determine an optimum dosing range for future animal studies and subsequent clinical trials. Based on these and prior results, the Company will be focusing its immediate development program on ovarian cancer and melanoma. The first of these animal studies is currently underway at the Ottawa Hospital Research Institute (“OHRI”) in ovarian cancer. Further testing of GAP-107B8 on melanoma is about to commence under the guidance of Dr. Gary Schwartz at Memorial Sloan Kettering Cancer Center in New York. GAP-107B8 showed a strong effect in both melanoma and ovarian cancers in both single-dose and 5-dose testing at the NCI. In addition, the Company and NCI staff will meet in late November to discuss these results and ways in which the NCI may participate in various aspects of the development program for GAP-107B8.

The results across such a wide range of cancer cell lines, including a number which are known to be resistant to standard chemotherapy, indicate that GAP-107B8 has the potential to become a new cancer drug with less toxic side effects than common chemotherapeutic regimens.

Robert McInnis, President of the Company, stated “We are very pleased with the extent of activity in the NCI panel, as this activity against all cell lines provides a wide range of development opportunities for us, and provides us with additional support for a focus on ovarian cancer and melanoma. Our objective of the testing at the NCI – independent and verifiable validation of activity – has been fully realized. Over the past 12 months we have made significant progress in moving our lead drug to clinical trials: generating quality- controlled gram-scale production of the compound; achieving verifiable independent validation of compound activity at both the NCI and here in Ottawa at the OHRI; and programs underway in the area of bioassay development, understanding of signalling pathways involved, and continued testing programs at Memorial Sloan Kettering. This progress is very encouraging to me and to our team. Most importantly, results so far indicate a potential for new hope for the future of patients suffering from several types of cancer”.

About The National Cancer Institute

The National Cancer Institute (NCI), located in Bethesda, MD is an institute of the National Institutes of Health, the primary U.S. Federal Agency for conducting and supporting medical research. The NCI has a mandate to select and screen novel drug compounds that could potentially make a material difference in the “war against cancer”. Selection to the NCI screening program is through a competitive application process. Details on the NCI’s compound screening program can be found at http://dtp.nci.nih.gov/. More general information on the NCI is found at www.cancer.gov.

About PharmaGap Inc.

PharmaGap Inc. (TSX VENTURE: GAP)(OTCBB: PHRGF), based in Ottawa, ON, is a biotechnology company with a core focus on developing novel peptide therapeutics for the treatment of cancer. PharmaGap’s GAP-107B8 is a novel peptide drug designed to inhibit the activity of protein kinase C (PKC), a cell signalling enzyme implicated in certain types and stages of cancer. Independent peer-reviewed research has demonstrated that over-expression of PKC plays a role in the development of many cancer types. For more information please visit www.pharmagap.com.

Note: Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release. No Securities Commission or other regulatory authority having jurisdiction over PharmaGap has approved or disapproved of the information contained herein. This release contains forward looking statements that may not occur or may change materially.

Contacts:
PharmaGap Inc.
Robert McInnis
President & CEO
613-990-9551
bmcinnis@pharmagap.com
www.pharmagap.com

SOURCE: PharmaGap Inc.

Posted under Cancer Research, Discoveries, Innovations and Patents, FDA News, New Products, Oncology Research, Press Releases | No Comments

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 Directorsâ€™ member Dr. Joseph Rubinfeld has accepted the additional responsibility of Chief Scientific Advisor, and will consult on all aspects of the Companyâ€™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, â€œWe 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.

â€œImportantly, we expect that we have ample financial resources with our current cash position and investment in RXi Pharmaceuticals Corporation to support this strategy,â€ according to Mr. Kriegsman. â€œWe 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, â€œHaving 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, â€œWe 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€

CytRxâ€™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^Â®) and second-line tyrosine kinase inhibitors (i.e. dasatinib (Sprycel^Â®) and nilotinib (Tasigna^Â®)). 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. CytRxâ€™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 Companyâ€™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 CytRxâ€™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.

Posted under Cancer Research, Clinical Trials, Compound Screening, Discoveries, Innovations and Patents, Drug Development, FDA News, Medicinal Chemistry, New Drugs, New Products, North America, Oncology Research, Press Releases, R & D, Research Projects, USA and Canada | No Comments

Definiens Releases TissueMap 2.0 for Advanced Oncology Research

Last Updated on Saturday, 15 December 2007 05:07 Written by admin Saturday, 15 December 2007 05:05

Munich, Germany â€“ December 6th, 2007 â€“ Definiens, the number one Enterprise Image Intelligenceâ„¢ company, today unveiled the release of Definiens TissueMap 2.0, highlighting the companyâ€™s focus on oncology research. The image analysis software application is especially designed for the detailed, automated morphometric quantification of biomarkers of nuclei or cell bodies in epithelial tumors or xenografts. The application features the detection of viable and necrotic tissue in xenografts, as well as regions of IHC (DAB) positively stained nuclei or cells in the viable tissue. This enables pathologists to automate the process of complex or highly apoptotic xenograft analysis in oncology research.

Effective imaging technologies support pharmaceutical development in oncology

The discovery and application of oncology biomarkers have enhanced opportunities for individual disease treatment by identifying new drug targets. They therefore have a significant impact on the entire process of drug development including the emergence and growth of imaging technologies utilized to acquire accurate measurements of disease parameters.
The effective use of imaging technologies, such as Definiens TissueMap 2.0, significantly improves the selection and prioritization of quality candidates early in the drug development pipeline. This results in substantial cost savings and faster time-to-market as poorer drug candidates are removed early in the discovery process.

Assessment of any biomarkers targeting an antigen located in the nucleus or cell body

Definiens TissueMap 2.0 reliably identifies areas and structures of interest in image data allowing researchers to distinguish between viable and necrotic tumor areas and to quantify markers. It offers:

o Full tissue slide analysis

o Fast and reproducible results

o Platform independence and connectivity

o Easy customization

o Precise measurement of morphological parameters

Definiens TissueMap 2.0 encompasses the assessment of any biomarkers targeting an antigen located in the nucleus such as proliferation markers (Ki67, PCNA, BrdU, etc.), apoptosis markers such as Cap3 as well as estrogen or progesterone receptors. Antibodies or markers co-/located in the cell body, such as cytokeratines (CD31, AE1/3, etc.) and other proteins (CD45, CD23 or similar) can also be evaluated.

Comprehensive software for quantification regardless of staining methodology

Definiens TissueMap 2.0 enables the quantification of biomarker expression patterns in image data regardless of staining methodology. The software application effectively analyzes image data in oncology research, including cases involving poor staining technique and data obtained from heterogeneous equipment.

Definiens TissueMap 2.0 enables the automated detection of relevant morphological structure in tissue and tumor sections. It improves research results through increased data accuracy, consistency and reproducibility.

New information concerning Definiens TissueMap 2.0 was presented at the 7th World Drug Discovery & Development Summit 2007 in Cologne, Germany, December 4-5, 2007, which brought together leading pharmaceutical and biotech professionals to discuss key scientific and strategic challenges.

Definiens in Life Sciences

By automating image analysis on an enterprise level, Definiens supports Life Science organizations to analyze and interpret vast numbers of images accurately and consistently. Definiens improves the measurement of cell assays, the examination of tissue samples and the interpretation of non-invasive imaging, enabling high-content screening, digital pathology and translational medicine.

About Definiens

Definiens is the number one Enterprise Image Intelligence company for analyzing and interpreting images on every scale, from microscopic cell structures to satellite images. The Definiens Cognition Network TechnologyÂ®, developed by Nobel laureate Prof. Gerd Binnig and his team, is an advanced and robust context-based technology designed to fulfill the image analysis requirements of the Life and Earth sciences markets. The technology is modeled on the powerful human cognitive perception processes to extract intelligence from images. Definiens provides organizations with faster image analysis results, allowing deeper insights enabling better business decisions. The company is headquartered in Munich, Germany and has offices throughout the United States. Further information is available at www.definiens.com.

Definiens, Definiens Cellenger, Definiens Cognition Network Technology, Definiens eCognition, Enterprise Image Intelligence and Understanding Images are trademarks or registered trademarks of Definiens.

Posted under BioInformatics, Europe, Oncology Research, Press Releases | No Comments

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