Achilles' heel in lethal prostate cancer discovered

An international research team has discovered a genetic Achilles’ heel in neuroendocrine prostate cancer-a vulnerability that researchers say can be attacked by a targeted drug that is already in clinical trials to treat other types of cancers.

Reporting their findings online in Cancer Discovery (Nov. 17, 2011), the authors say the investigational Aurora kinase inhibitor PHA-739358 had a dramatic response in animal models of neuroendocrine prostate cancer.

The findings "are very exciting, because our bench-to-bedside approach identified a new molecular target for a subtype of prostate cancer for which a drug is now available," said senior author Mark A. Rubin, MD, of New York-Presbyterian Hospital/Weill Cornell Medical Center, New York.

The finding is especially important because many men are now being treated with new, highly potent androgen suppression therapy, which the authors believe will significantly increase the risk of future development of neuroendocrine tumors.

Although most of the men who die of advanced prostate cancer each year have been treated with androgen suppression therapy, it is impossible to know how many of them developed neuroendocrine tumors because patients are not usually biopsied at that stage of their disease, the authors say. Studies to define changing biology in prostate cancer are only now starting.

"Still, there is evidence to suggest that androgen suppression results in a more aggressive cancer in a growing number of men, and now, with this study, we may have a way to treat these patients," said lead author Himisha Beltran, MD, also of New York-Presbyterian Hospital/Weill Cornell Medical Center.

The study demonstrated that PHA-739358 worked against human neuroendocrine prostate cells in the laboratory, and that it had a dramatic response in mouse models of neuroendocrine prostate cancer. It shrank large tumors to very small sizes in a short period of time, compared with untreated mice. There was also significantly enhanced sensitivity of neuroendocrine prostate cancer compared to prostate adenocarcinoma, the researchers reported.

"Not only are we eager to test the drug in patients diagnosed with neuroendocrine prostate cancer, we hope to develop biomarkers that can help us screen patients for these cells before the cancer advances," Dr. Beltran said.

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