Home  |  Top News  |  Most Popular  |  Video  |  Multimedia  |  News Feeds  |  Feedback
  Medicine  |  Nature & Earth  |  Biology  |  Technology & Engineering  |  Space & Planetary  |  Psychology  |  Physics & Chemistry  |  Economics  |  Archaeology
Top > Medicine, Health Care > Scientists Test 5,000 Combinations of… >
Scientists Test 5,000 Combinations of 100 Existing Cancer Drugs to Find More Effective Treatments

Published: November 7, 2012.
By ECCO-the European CanCer Organisation
http://www.ecco-org.eu

Scientists in the United States have tested all possible pairings of the 100 cancer drugs approved for use in patients in order to discover whether there are any combinations not tried previously that are effective in certain cancers.

Dr Susan Holbeck (PhD), a biologist in the Division of Cancer Treatment and Diagnosis at the National Cancer Institute (USA) will tell the 24th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, today (Wednesday) that she and her colleagues have completed testing the 100 drugs, with 300,000 experiments to test the 5000 possible drug combinations in a panel of 60 cell lines developed by the National Cancer Institute (NCI-60 panel). "The goal is to identify novel drug combinations that are more active than the single agents alone. Since these are all approved agents, there is the potential to rapidly translate these combinations into the clinic," she will say.

Cancer treatments often use a combination of drugs, as a single drug rarely produces a long-lasting response due to the cancer becoming drug resistant. Some drug combinations have evolved over time by incorporating new agents into existing standards of care, while many newer treatments try to select combinations of drugs that target particular pathways that are known to be involved in the development of the cancer. However, some combinations can be so toxic that they have to be used at lower doses that may not be effective against the cancer.

"In addition, there are a large number of drug combinations that have never been used together in people, and for which there is no experimental information on whether there might a benefit to the combination," said Dr Holbeck. "We decided that it would be a feasible project to generate experimental data for all 5000 possible combinations of pairs, and that we would make these data available to all to enable additional experiments in support of taking new combinations to clinical trials.

"In order to provide a resource for understanding the efficacy of drug combinations, we have undertaken a systematic screening of most small molecule oncology drugs approved in the US, each in combination with all the others. This was done using a panel of human tumour cell lines derived from nine different types of cancer.

"We chose to test the combinations in the NCI-60 panel – a group of diverse cell lines that our programme has used for many years to screen potential new drugs – because we have a lot of information about these cell lines. For instance, mutations, gene expression, microRNA expression and so on have all been characterised, and this enables us to analyse the cell lines that benefit from a particular combination and potentially identify markers in those cell lines that might also be used as biomarkers in patients."

The researchers have found that some combinations have shown benefit in many cell lines, while others are active in just a few cell lines. When some of the new combinations were tested in human tumours grafted into mice, they were found to be more effective than the most active doses of single drugs.

"These results are promising but we need to repeat and confirm them," said Dr Holbeck. "Our goal is to rapidly translate several novel combinations into clinical trials. There will be many more leads than we can possibly follow through on. Once these data are published, the dataset, and tools to analyse it, will be made available on our web site for all to utilise as they wish.

"To our knowledge this is the first systematic characterisation of approved drugs in a large number of cancer cell lines. We are not making any assumptions about which combinations will give improved activity. The use of many diverse cancer cell lines allows data mining for markers of response that would not be possible with a small set of cell lines.

"Many groups are focusing on 'rational' combinations, i.e. making scientific inferences about which pathways it might make sense to block simultaneously with different drugs. We took a step back, and took an approach that tests all possible drug pairs. This allowed us to test not only the rational combinations, but also to explore drug pairs that otherwise would likely never be tested together."

Professor Stefan Sleijfer, the scientific chair of the EORTC-NCI-AACR Symposium, from Erasmus University Medical Centre (The Netherlands), commented: "This study is interesting because of the use of combinations of drugs already approved and on the market, which were tested in cell lines that have been well characterised in terms of genetic profiles. If confirmed, this study will form a basis for future clinical trials on such combinations in well-defined patient groups."


Show Reference »


Translate this page: Chinese French German Italian Japanese Korean Portuguese Russian Spanish


 
All comments are reviewed before being posted. We cannot accept messages that refer a product, or web site.If you are looking for a response to a question please use our another feedback page.
Related »

Cancer 
3/28/12 
Writing the Book of Cancer Knowledge
By Broad Institute of MIT and Harvard
The goal of cancer treatment is to match the right drug to the right target in the right patient. But before such "personalized" drugs can be developed, more knowledge …
Cell 
3/28/12 
Novartis Launches the Cancer Cell Line Encyclopedia to Catalog World's Cancer Cell Lines
By Novartis Institutes for BioMedical Research
Novartis and the Broad Institute have developed a cancer cell line encyclopedia that catalogues the genetic and molecular profiles of almost 1,000 human cancer cell lines used in drug …
Trust 
7/15/10 
★★★★ 
Largest Study of Genomes And Cancer Treatments Releases First Results
By Wellcome Trust Sanger Institute
The largest study to correlate genetics with response to cancer drugs releases its first results today. The researchers behind the study, based at Massachusetts General Hospital Cancer Center and …
Studies 
12/2/13 
The Importance of Standardizing Drug Screening Studies
By Institut de recherches cliniques de Montreal
Montréal, December 2, 2013 – A bioinformatics expert at the IRCM, Benjamin Haibe-Kains, recently published an article stressing the importance of standardizing drug screening studies in the prestigious scientific …
Drugs 
7/15/13 
Scientists at NCI Generate Largest Data Set of Cancer-related Genetic Variations
By American Association for Cancer Research
PHILADELPHIA — Scientists at the National Cancer Institute (NCI) have generated a data set of cancer-specific genetic variations and are making these data available to the research community, according …
Cancer 
9/25/14 
New Research Outlines Promising Therapies for Small Cell Lung Cancer
By University Hospitals Case Medical Center
CLEVELAND: Two recently published studies by a research team at University Hospitals (UH) Case Medical Center Seidman Cancer Center have the potential to advance treatments for small cell lung …
Cancer 
1/6/14 
New Technique Targets Specific Areas of Cancer Cells with Different Drugs
By North Carolina State University
Researchers have developed a technique for creating nanoparticles that carry two different cancer-killing drugs into the body and deliver those drugs to separate parts of the cancer cell where …
More » 
 
© Newsline Group  |  About  |  Privacy Policy  |  Feedback  |  Mobile  |  Japanese Edition