Researchers Identify Possible New Target for Treating Neuroendocrine Prostate Cancer

Researchers at UCLA are reporting that prostate adenocarcinoma and neuroendocrine prostate cancer can arise from a common epithelial clone. In addition, the findings point to some specific targets for therapeutic intervention. Writing in the journal Cancer Cell, the researchers report that an experimental drug called CD532 may help reduce tumor size in men who have neuroendocrine prostate cancer.  

The findings are particularly important because neuroendocrine prostate cancer does not respond to standard treatments. Men who are diagnosed with the disease typically live for less than 12 months following diagnosis.  Approximately one-fourth of men who die of prostate cancer have the neuroendocrine subtype.

“Identifying the cellular changes that happen in cancer cells is key to the development of drugs that inhibit those changes and thereby stop the progression of the disease,” said lead study author Owen Witte, MD, founding director of the UCLA Broad Stem Cell Research Center, in a news release.

The researchers obtained noncancerous prostate basal cells, which contained prostate stem cells from men who underwent prostate surgery. They added a gene called MYCN to those cells. MYCN produces a protein called N-Myc, which is known to play a role in several types of aggressive cancer. In prostate cancer, N-Myc appears to turn less aggressive prostate cancer cells into the cancer stem cells that form the aggressive neuroendocrine prostate cancer tumors.

The researchers transplanted the basal cells with the added MYCN genes into mice. Those cells with elevated N-Myc levels grew into neuroendocrine prostate cancer tumors. The researchers found that N-Myc is essential for tumor maintenance in tumors initiated by N-Myc and AKT1. In addition, they found evidence that destabilization of N-Myc through Aurora A kinase inhibition induces tumor cell death.

CD532 works by changing the structure of the protein Aurora A kinase, which stabilizes N-Myc. CD532 had been in development for some time for a type of childhood nervous system cancer in which N-Myc also plays a role. The drug had been shown in preclinical studies to have promise for treating that disease, but it had not previously been tested for neuroendocrine prostate cancer.

In the current study, CD532 effectively destabilized N-Myc and suppressed the neuroendocrine tumors’ growth. The investigators hope to next identify other drugs that may be effective for treating neuroendocrine prostate cancer based on these findings. CD532 has only been used in preclinical tests and has not been tested in humans.