Temporal Evolution of N-Myc Signaling and Early Targeting of the Neuroendocrine Phenotype in Prostate Cancer
Abstract
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-Myc/Aurora 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).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2018
- Accession Number
- AD1095906
Entities
People
- David Rickman
- Himisha Beltran
Organizations
- Weill Cornell Medicine