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The development of effective anti-androgen therapies for prostate cancer is a major scientific advance. However, some men who receive these targeted treatments are more likely to develop a deadly treatment-resistant prostate cancer subtype called neuroendocrine prostate cancer (NEPC). No effective treatment for NEPC exists.
Scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified how prostate cancertransforms into aggressive NEPC following treatment with anti-androgen therapy. Their findings which include the metabolic rewiring and the epigenetic alteration that drives this switch reveal that an FDA-approved drug holds potential as a NEPC treatment. The research also uncovers new therapeutic avenues that could prevent this transformation from occurring.
“Acquired treatment resistance is a major concern for every oncologist. Eventually, over enough time, cancer patients who receive a targeted therapy can become resistant to treatment,” says Darren Sigal, M.D., an oncologist at Scripps Clinic and Scripps MD Anderson Cancer Center who worked with the scientists on the study. “This study is an important advance that helps us understand why targeted treatments for prostate cancer may promote the development of a more aggressive tumor. These insights could lead to better treatments that help fathers, sons and grandfathers around the world who are fighting prostate cancer.”
Prostate cancer is the second-leading cause of cancer death for American men, according to the American Cancer Society. The cancer grows in response to hormones called androgens. Targeted therapies that block these hormones have extended survival for many patients. However, nearly all men eventually develop resistance to these treatments. In 2019, more than 30,000 men in the U.S. are expected to die from prostate cancer.
“Similar to bacteria that gain resistance to antibiotics, tumors can become resistant to anti-cancer drugs by ‘remodeling’ their environment and developing strategies to evade targeted therapies. As targeted therapies become more potent, putting more stress on tumors, we expect to see drug resistance become more common,” says Maria Diaz-Meco, Ph.D., the senior author of the paper and a professor in the Cancer Metabolism and Signaling Networks Program at SBP. “Our study shows that in a form of treatment-resistant prostate cancer, a tumor suppressor gene called protein kinase C lambda/iota is downregulated. We subsequently identified metabolic and epigenetic vulnerabilities which are possible routes to prevent treatment resistance from arising.”