Potential New Options for Neuroendocrine Prostate Cancer

April 2011, Vol 2, No 2 - Genitourinary Cancers Symposium

Orlando, FL—Very little is known about the underlying biology of neuroendocrine prostate cancer, an aggressive form of the disease that can arise on its own or from an existing prostate adenocarcinoma. Patients typically die within 1 year of diagnosis, despite aggressive chemotherapy. New research suggests a clonal origin of neuroendocrine prostate cancers from prostate adenocarcinoma and possible treatment targets.

Himisha Beltran, MDAt the 2011 Genitourinary Cancers Symposium, Himisha Beltran, MD, a fellow at Weill Cornell Medical College, NY, reported about the use of next-generation RNA sequencing and oligonucleotide arrays to profile neuroendocrine prostate cancer, prostate adenocarcinoma, and benign prostate samples to assess for specific gene expression. “We found Aurora kinase A changes in neuroendocrine prostate cancers,” Dr Beltran said. She was presented with the Merit Award for Young Scientists at the meeting.

Aurora kinase A, a cell-cycle kinase, was overexpressed in the neuroendocrine prostate cancer samples, and included a gene amplification of Aurora kinases and N-myc.

“The functional distribution shows they cooperate and can induce the neuroendocrine phenotype in adenocarcinoma cells involved in progression,” Dr Beltran said.

Only 5% of the prostate adenocarcinoma samples had an Aurora kinase or N-myc alteration, and it was not found in any of the benign samples.

The researchers observed in vitro and in vivo sensitivity to the Aurora kinase inhibitor PHA-739358 in the neuroendocrine prostate cancer samples but not in the adenocarcinoma samples. Neuroendocrine marker expression was suppressed in the treated xenografts.

“Treatment with a kinase inhibitor should prove effective for neuroendocrine prostate cancer,” Dr Beltran concluded.