Neuroendocrine marker expression suppressed by treatment with Aurora kinase inhibitor
THURSDAY, Nov. 17 (HealthDay News) -- AURKA and MYCN are overexpressed in patients with neuroendocrine prostate cancers (NEPC) and cooperate to produce a neuroendocrine phenotype, according to a study published in the November issue of Cancer Discovery.
Himisha Beltran, M.D., from the Weill Cornell Medical College in New York City, and colleagues sought to identify molecular transformations of NEPC. A total of seven NEPC, 30 prostate adenocarcinoma (PCA), and five benign prostate tissue (BEN) samples were profiled using next-generation RNA sequencing and oligonucleotide assays. The results were validated in a larger cohort of 37 patients with NEPC, 169 with PCA, and 22 patients with BEN through immunohistochemistry and fluorescence in situ hybridization.
The investigators found that 40 percent of NEPC and 5 percent of PCA tumors showed significant overexpression and gene amplification of AURKA and MYCN, and found evidence that they work together to produce a neuroendocrine phenotype in prostate cells. NEPC, and PCA with overexpressed MYCN, showed increased sensitivity to in vitro and in vivo therapy with an Aurora kinase inhibitor. Following treatment, neuroendocrine marker expression was completely suppressed.
"Based on the biologic role of AURKA in NEPC, its interaction with MYCN, and the dramatic and preferential sensitivity of NEPC preclinical models to AURKA inhibition, we propose that AURKA inhibitors may potentially benefit patients with these molecular alterations," the authors write.
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