Discovery of New Prostate Cancer Biomarkers Could Improve Precision Therapy; SPOP Mutations Confer Resistance to BET Inhibitors

Mayo Clinic researchers have identified a new cause of treatment resistance in prostate cancer. Their discovery also suggests ways to improve prostate cancer therapy. The findings were published online on August 14, 2017 in Nature Medicine. The article is titled “Prostate Cancer–Associated SPOP Mutations Confer Resistance to BET Inhibitors Through Stabilization of BRD4.” In the publication, the authors explain the role of mutations within the SPOP gene on the development of resistance to one class of drugs. SPOP mutations are the most frequent genetic changes seen in primary prostate cancer. These mutations play a central role in the development of resistance to drugs called BET-inhibitors. BET (bromodomain and extra-terminal domain) inhibitors are drugs that prevent the action of BET proteins. These proteins help guide the abnormal growth of cancer cells. As a therapy, BET-inhibitors are promising, but drug resistance often develops, says Haojie Huang, PhD, senior author and a molecular biologist within Mayo Clinic's Center for Biomedical Discovery. Prostate cancer is among the most frequently diagnosed malignancies in the United States. It is also the third leading cause of cancer death in American men, according to the American Cancer Society. Because of this, says Dr. Huang, improving treatments for prostate cancer is an important public health goal. In the publication, the authors report SPOP mutations stabilize BET proteins against the action of BET-inhibitors. By this action, the mutations also promote cancer cell proliferation, invasion, and survival.
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