Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets

Using next-generation RNA sequencing and oligonucleotide arrays, 7 neuroendocrine prostate cancers, 30 prostate adenocarcinomas and 5 benign prostate tissues were profiled, with validation on a larger cohort of 37 neuroendocrine cancers, 169 adenocarcinomas and 22 benign tissues using immunohistochemistry and fluorescence in situ hybridisation. Significant overexpression and gene amplification of AURKA and MYCN were found in 40% of neuroendocrine prostate cancers and 5% of adenocarcinomas, with evidence that they cooperate to induce a neuroendocrine phenotype in prostate cells. Neuroendocrine cancers, and MYCN-overexpressing adenocarcinomas, were dramatically sensitive to Aurora kinase inhibitor therapy in vitro and in vivo, with complete suppression of neuroendocrine marker expression after treatment.