Targeting the fibroblast growth factor pathway in molecular subtypes of castration-resistant prostate cancer

Androgen receptor (AR) pathway inhibition remains the cornerstone for first- and second-line prostate cancer therapies. Although AR signaling inhibitors, such as enzalutamide and abiraterone extend survival in recurrent and castration-resistant prostate cancer (CRPC), durable and complete responses are rare. Resistance mechanisms employed by metastatic CRPC include amplification of AR and AR splice variants in AR-positive CRPC (ARPC) and conversion to AR-null phenotypes, such as double-negative prostate cancer (DNPC) and small cell or neuroendocrine prostate cancer (SCNPC). We have shown previously that DNPC can bypass AR-dependence through fibroblast growth factor (FGF) signaling. However, the role of the fibroblast growth factor receptor (FGFR) pathway in other molecular subtypes of CRPC has not been elucidated. Overall design: RNA sequencing of prostate tumor patient-derived xenograft (PDX) models, prostate tumor cell lines, and CRPC metastases using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500 and NovaSeq 6000.