Late Stage Prostate Cancer Therapy

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Hormone therapies are a popular approach in the treatment of prostate cancer. Their goal is to either reduce or stop androgens in the body from affecting prostate cells. Prostate cancer depends on the male sex hormone, testosterone, to grow.

But a problem this course of treatment encounters is the resistance to it that the body inevitably builds up over time. In fact, almost 100 percent of prostate cancer patients will eventually develop a resistance to hormone therapies. That translates to around 32,000 new cancer cases becoming resistant, lessening the likelihood of survival, in the U.S. alone.

Now a start-up company, Resarci Therapeutics, founded by professors and post-doctoral fellow from Purdue University think they have this problem licked. Their strategy is to target the cholesterol metabolism instead of the androgen pathway.

"By targeting the cholesterol metabolism, which is specific to cancer cells and independent of the hormone signaling pathway, we are able to eliminate the hormone resistance," said Junjie Li, a postdoc research fellow in Purdue's Weldon School of Biomedical Engineering. "We target the aberrant cholesterol metabolism using an inhibitor of cholesterol esterification enzyme ACAT-1, named avasimibe. Avasimibe selectively kills cancer cells by preventing the cholesteryl ester accumulation and inducing free cholesterol related toxicity in cancer cells."

The team has been working with mouse models, and found that the inhibitor avasimibe was able to overcome resistance to hormone therapy in those trials. That particular biochemical significantly reduces plasma total triglyceride and VLDL cholesterol (one of the “bad” types of cholesterol.

“We want to improve the formulation of our product, test it in pre-clinical settings and launch an early-stage clinical trial,” said Timothy L. Ratliff, director of Purdue’s Center for Cancer Research. “We are applying for funding from NIH and other agencies, but are also looking for investors or potential partnerships with pharmaceutical companies.”