Therapeutic Targeting of Neuroendocrine Prostate Cancer
Abstract
Increased incidence of treatment induced neuroendocrine prostate cancer (NEPC) is particularly alarming as this diagnosis is associated with poor prognosis and decades of cytotoxic chemotherapy as the only treatment option. We previously identified neuronal transcription factor BRN2 as a potent driver of neuroendocrine differentiation and an attractive target in NEPC. Our goal is to Evaluate the mechanism by which BRN2 alters chromatin architecture to support neuroendocrine lineage reprogramming. To facilitate any future clinical use of a BRN2 inhibitor in PCa, the project described herein aimed to identify a biomarker of BRN2 positive (BRN2+) NEPC that can be readily detected in serum from patients. This would enable longitudinal monitoring of patients for development of BRN2+ NEPC, similarly to how prostate-specific antigen (PSA) levels are currently monitored to gauge PCa progression, and thus potentially provide the means for early detection of PCa patients who may benefit from a BRN2 inhibitor. This report documents progress made towards this aim. Using unbiased approach by combining ChIPseq, RNAseq and secreted protein analysis, we identified Neuronal pentraxin 1 (NPTX1) as a promising biomarker and validated that it can be detected in serum from PCa patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2022
- Accession Number
- AD1190848
Entities
People
- Colm Morrissey
Organizations
- University of Washington