BioCentury
ARTICLE | Preclinical News

Papers uncover predictive markers for BET inhibitor responses

August 14, 2017 3:24 PM UTC

A trio of papers published in Nature Medicine today challenge the notion that similar mutations in the same gene can predict the same drug responses across different types of cancer. While two separate teams of U.S. and Chinese researchers uncovered a link between mutations in speckle-type POZ protein (SPOP) and BET inhibitor resistance in prostate cancer, a third group found that mutations in the same domain of the SPOP gene actually sensitized endometrial cancers to the drugs.

Inhibitors of epigenetic modulating bromodomain and extraterminal domain (BET)-containing proteins are moving through the clinic for cancer, with MK-8628 from Merck & Co. Inc. (NYSE:MRK) and Mitsubishi Tanabe Pharma Corp. (Tokyo:4508) in Phase II for brain cancer and eight other inhibitors following in Phase I or preclinical testing. However, drug resistance to the inhibitors has been noted and resistance mechanisms are poorly understood...