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Breast cancer study suggests new drug targets and combinations

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New Delhi | Friday, Jan 15 2016 IST
The largest analysis of breast cancer cell function to date suggests dozens of new uses for existing drugs, new targets for drug discovery, and new drug combinations, besides pointing out the mechanisms by which cancer cells resist treatment. The study results have been published online in the journal Cell.Led by researchers from the NYU Langone Medical Centre, its Laura and Isaac Perlmutter Cancer Centre, and the Princess Margaret Cancer Centre in Toronto, the team reached its conclusions by combining genetic analyses of more breast cancer cell types than studied previously, new statistical methods, and comparisons with databases of molecular signatures and the effects of anti-cancer drugs.Unlike earlier algorithms, the new statistical model was able to identify several previously known genes that are essential for specific breast cancer subtypes.Better detection and therapy have led to greater than 85 per cent 5-year survival in breast cancer, yet half of those affected still die from the disease. Limits on treatment success so far reflect a lack of understanding of the complex networks of molecular changes that enable most cancers to persist in the face of treatments that address any single disease mechanism.For many years, labs worldwide have conducted large-scale genomic studies seeking to identify the many genetic changes that contribute to breast cancer. While such studies have yielded information on which genetic changes are found in different types and subtypes of cancer, they have been less successful in determining which of these changes are critical to cancer cell proliferation and survival, or how these changes might be exploited by therapies.To complement genomic studies, many labs in recent years had turned to shRNA "dropout screens," which shut down each gene in a cancer cell one by one to see which are most important to its survival. Most past studies, however, did not examine enough cell lines to capture the landscape of diverse changes seen across breast cancer as a whole.The combined methods created newfound signals in the data more closely tied to impact on cancer cell traits and did a better job screening out false positives. The study identified a number of candidate genes previously unknown to play a role in breast cancer cell survival. In addition, the team found clusters of genes that were required in cells that were either sensitive or resistant to 90 anti-cancer drugs.Among the new and potential "druggable" targets identified for triple negative breast cancer, the most deadly form of the disease.The data also suggested for additional study dozens of new, potential drug combinations for the treatment of breast cancer subtypes, including RAF/MEK and CDK4 inhibitors, EGFR inhibitors and BET-inhibitors with epirubicin and vinorelbine, and PLK1 inhibitors with AKT inhibitors."Very few patients today get a whole genome sequence analysis done on their cancer cells, and the few that do typically receive little medical benefit from the results," says lead study author Benjamin Neel, director of the Perlmutter Cancer Centre.UNI YSG SV 0830

-- (UNI) -- C-1-1-DL0140-539204.Xml

 
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