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Temporal Evolution of N-Myc Signaling and Early Targeting of the Neuroendocrine Phenotype in Prostate Cancer

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Technical Report,30 Sep 2017,29 Sep 2018

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Weill Medical College of Cornell University New York United States

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Transformation of castration resistant prostate cancer CRPC towards androgen signaling independence has emerged as a resistance mechanism in a subset of metastatic CRPC following exposure to androgen receptor AR-targeted therapies such as abiraterone or enzalutamide. Clinically, patients typically present with progression in the setting of a low or modestly rising serum prostate specific antigen PSA and metastatic biopsies can show pathologic or molecular features consistent with neuroendocrine prostate cancer NEPC. NEPC is associated with low or absent AR expression, suppressed AR signaling, retention of early genomic mutations from its adenocarcinoma precursor, and acquisition of distinct genomic and epigenomic alterations Beltran H, et al, Nature Medicine, 2016. The development of novel therapeutic approaches for patients with NEPC represents a clinical unmet need. Over the last seven years, our group has focused on characterizing the molecular landscape of NEPC and have identified and validated new therapeutic targets, including the N-MycAurora A pathway and specific epigenetic modifiers such as Enhancer of Zeste Homolog 2 EZH2 Beltran H, Rickman DS et al Cancer Discovery 2011 Dardenne E, Beltran H, . and Rickman DS, Cancer Cell 2016.

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  • Medicine and Medical Research

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