URMC cancer research may prolong lives

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A microscopical view of prostate cancer cells. (Photo: National Cancer Institute/Otto Brawley)

University of Rochester Medical Center researchers have unlocked a genetic key that could extend the life of some late-stage prostate cancer patients.

The second-leading cause of death among men, prostate cancer can be relatively mild for some, staying confined to the organ, growing very slowly and posing almost no risk for years. But cancers that have turned aggressive, spreading from the prostate to bones or other organs, are another matter.

In addition to causing pain and suffering, aggressive forms of cancer also become increasingly resistant to treatment. 

A first line of defense against prostate cancer is hormone therapy, which starves metastatic cancer cells of the androgens they need to grow. Next comes chemotherapy, which kills cancer cells. But cancer cells eventually seem to figure out workarounds to defeat both therapies, learning to thrive in the face of modern medicine’s best shots to defeat them.

Since its 2012 approval by the U.S. Food and Drug Administration, a drug called enzalutamide has helped prostate cancer patients who otherwise have reached the end of the line in treatment options by reinvigorating the body’s ability to starve increasingly aggressive cancer cells of the androgens they need to grow. 

The effectiveness of enzalutamide against such late-stage metastatic prostate cancer has upended previous science, which had concluded that hormone blocking ceased to work at all once cancer had progressed to that point. 

Enzalutamide’s benefits are short-lived, however, providing only five months more of life on average to end-stage patients. To make matters worse, once cancers shrug off enzalutamide’s androgen-blocking effect, they become even more aggressive.

That might change with a discovery made by a team working in the laboratory of researcher Chawshang Chang, UR’s George Hoyt Whipple Distinguished Professor of pathology, urology and radiation oncology. 

Led by Jie Lou, a UR graduate student in biology, the research team focused on an unfortunate side effect of enzalutamide, an increase in neuroendocrine cells in tumors. Such cells, which can form in several varieties of cancerous tumors, interact with hormones. In prostate cancer, they provide a path for tumors to get the androgens cancer cells need to grow and proliferate and thus override enzalutamide’s androgen-blocking effect. 

Specifically, the Chang and Lou team uncovered a mechanism that switches the function of a key gene to make it induce formation of neuroendocrine cells. A drug that defeats that switch is being tested, but trials so far only shown it to be effective in mice. Further work is needed before it might be available to human patients. 

Still, says Edward Messing M.D., a nationally recognized specialist treating urologic cancers at UR Medicine’s James P. Wilmot Cancer Center, “Dr. Chang’s team has identified an important molecular mechanism that affects many of the thousands of men with advanced prostate cancer. Understanding and reversing the switch that causes neuroendocrine differentiation should prolong the lives of these men and significantly reduce their suffering.” 

study published earlier this month in the journal Nature Communications details the URMC team’s discoveries. 

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