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. 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.