Abstract 5901: The role of POU3F2 in the aggressive behavior of neuroendocrine prostate cancer

Neuroendocrine and Small Cell Prostate Cancer (NEPC) is a lethal disease emerging from Castrate Resistant Prostate Cancer (CRPC) after treatment with next-generation anti-androgen therapies such as abiraterone and enzalutamide. The mechanisms by which treatment resistant prostate epithelial cancer cells trans-differentiate to poorly differentiated small cell cancer are not well understood. We and others found that Nervous System-Specific Octamer-Binding Transcription Factor (POU3F2) expression is induced in NEPC. POU3F2 is a reprogramming transcription factor that controls cellular differentiation and can induce stem-like cells from differentiated glioblastoma. POU3F2 also plays a critical role in melanoma progression and in small cell carcinoma of the lung. NEPC shares similarities with small cell carcinoma from other organs. We hypothesized that POU3F2 may be a key transcription factor that is required for transdifferentiation and the survival of NEPC cells. We further hypothesize that the underlying mechanism of therapy resistance in NEPC is that NEPC consists of stem-like cells that were reprogrammed from differentiated prostate cancer cells under the selective pressure of androgen receptor (AR) pathway-targeted therapy. We elucidated the functional role of POU3F2 in the aggressive cancer behavior of NEPC —including stem-cell properties, tumorigenesis, invasion, and chemo-resistance. We also characterized the mechanisms that regulate POU3F2 expression in therapy-resistant NEPC. The study provides a rational for targeted therapy for treatment of NEPC. It could also be used to design a strategy to halt the emergence of NEPC from CRPC. Citation Format: Naoko Kobayashi, Dai Hong, Chun Wang, Joyce Yamashiro, Johnny Guan, Robert E. Reiter. The role of POU3F2 in the aggressive behavior of neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5901.