Cancer Discov. 2011 Nov; 1(6): 487-495
Beltran H, Rickman DS, Park K, Chae SS, Sboner A, Macdonald TY, Wang Y, Sheikh KL, Terry S, Tagawa ST, Dhir R, Nelson JB, de la Taille A, Allory Y, Gerstein MB, Perner S, Pienta KJ, Chinnaiyan AM, Wang Y, Collins CC, Gleave ME, Demichelis F, Nanus DM, Rubin MA
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer which most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing as well as oligonucleotide arrays, you profiled 7 NEPC, 30 PCA, as well as 5 benign prostate tissue (BEN), as well as certified findings upon tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC as well as FISH. We discovered significant overexpression as well as gene amplification of AURKA as well as MYCN in 40% of NEPC as well as 5% of PCA, respectively, as well as evidence which that they cooperate to induce a neuroendocrine phenotype in prostate cells. There was dramatic as well as enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase inhibitor therapy both in vitro as well as in vivo, with complete suppression of neuroendocrine marker expression following treatment. We propose which alterations in Aurora kinase A as well as N-myc are involved in a development of NEPC, as well as future clinical trials will help establish from a efficiency of Aurora kinase inhibitor therapy.
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