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New compound could combat castration-resistant prostate cancer

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Researchers at Sanford-Burnham Medical Research Institute may have hit on the next big thing in prostate cancer treatment. They've developed a compound called SMIP004 that works by zeroing in on prostate cancer cells and compromising their ability to withstand environmental stress--a trademark of cancer cells.

Prostate cancer is the second most common cancer and the second leading cause of cancer-related death among men in the United States.

The standard of care for prostate cancer has made leaps and bounds in the past few decades--first with the introduction of the serum PSA test to screen for the disease. Now, treatment options include new surgical approaches, radiotherapy, chemotherapy and hormonal therapy. One treatment option for prostate cancer patients is castration, which reduces the production of the male sex hormone testosterone. Castration-resistant prostate cancer is common though, and in these patients, the cancer cells can adapt and become unresponsive to hormone deprivation therapy.

"For advanced prostate cancer--castration-resistant prostate cancer in particular--when the cancer recurs, the only therapy is Taxol, which will prolong life for only a couple of months," said senior study author Dr. Dieter Wolf, director of the National Cancer Institute-designated Cancer Center proteomics facility at Sanford-Burnham.

Wolf and his team found that SMIP004 works by interfering with the functioning of mitochondria, the powerhouse center of cells. During a process known as oxidative stress--which cancer cells are exposed to when cancer-causing genes are activated--harmful molecules called reactive oxygen species (ROS) build up within mitochondria. This buildup causes cells to stop replicating and die.

SMIP004 acts on the androgen receptor, making it particularly promising for castration-resistant prostate cancer, Wolf said. Through one of the newly identified pathways triggered by oxidative stress, SMIP004 caused a decrease in the number of androgen receptors--proteins located in prostate cancer cells that are activated by testosterone. Cancer cells manage to survive in castration-resistant prostate cancer by increasing the production of androgen receptors.

Prostate cancer, especially castration-resistant cancer, has been of interest to pharma companies in recent years. Johnson & Johnson's ($JNJ) Zytiga has been competing with Xtandi, a new prostate cancer therapy marketed by Medivation ($MDVN) and Astellas. In June, J&J acquired Aragon Pharmaceuticals and its promising next-gen prostate cancer drug ARN-509 for $650 million in cash and up to $350 million in milestones.

- here's the press release

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