Nov. 29, 2011 A recent report in Cancer Discovery, a journal of the American Association for Cancer Research, suggests that a new treatment may be on the horizon for neuroendocrine prostate cancers, the most lethal subtype of this disease.
Mark Rubin, M.D., professor of pathology and laboratory medicine at Weill Cornell Medical College, said although fewer than 2 percent of men with prostate cancer present with neuroendocrine prostate cancer, the more common prostate adenocarcinoma can also evolve into a neuroendocrine prostate cancer, and the prognosis is grim.
"This is a highly lethal form of prostate cancer," said Rubin. "It is also rare enough that it's hard to get samples. This study is the largest of its kind, and it shows that we may be able to treat this highly aggressive disease."
Rubin and colleagues used next-generation RNA sequencing to profile samples of seven neuroendocrine prostate cancers, 30 prostate adenocarcinomas and five benign samples of prostate tissue.
They found that the genes AURKA and MYCN were overexpressed and amplified in 40 percent of neuroendocrine prostate cancers and in 5 percent of prostate adenocarcinomas.
Moreover, the researchers found that treatment with the investigational aurora kinase (AURKA) inhibitor PHA-739358 inhibited the growth of these neuroendocrine tumors.
Rubin said that PHA-739358 has been studied in prostate cancers before without success, but this may be due to the fact that previously studied prostate cancers were not neuroendocrine cancers.
"Prostate cancer is not a homogenous disease. We need to continue to sort out the aggressive disease from the indolent and treat accordingly," said Rubin.
The study was funded by the Prostate Cancer Foundation, the Ann and William Bresnan Foundation, the Early Detection Research Network and the Department of Defense.
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- H. Beltran, D. S. Rickman, K. Park, S. S. Chae, A. Sboner, T. Y. MacDonald, Y. Wang, K. L. Sheikh, S. Terry, S. T. Tagawa, R. Dhir, J. B. Nelson, A. de la Taille, Y. Allory, M. B. Gerstein, S. Perner, K. J. Pienta, A. M. Chinnaiyan, Y. Wang, C. C. Collins, M. E. Gleave, F. Demichelis, D. M. Nanus, M. A. Rubin. Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets. Cancer Discovery, 2011; 1 (6): 487 DOI: 10.1158/2159-8290.CD-11-0130
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