LAUSR

Prostate Cancer (PCa) is one of the most commonly diagnosed malignancies in men. Patients with advanced metastatic PCa have effective treatment options, but none of them are curative. Androgen deprivation is the most effective therapy, but growth of the cancer resumes over time in most cases, and the disease progresses to castration-resistant PCa (CRPC). Bone is the main site of CRPC progression. Acquired (or inherent) resistance mechanisms to second line therapy options for CRPC eventually lead to disease recurrence and, ultimately, death. The underlying mechanisms of PCa progression to first or second line therapy options are diverse and include fibroblast growth factor (FGF) axis activation. Indeed, we previously reported that blockade of FGFRs with dovitinib (TKI258) (Novartis Pharmaceuticals), a receptor tyrosine kinase inhibitor (TKI) with potent activity against FGFR1-3 and vascular endothelial growth factor receptor (VEGFR) has clinical activity in men with CRPC and bone metastases (PMID: 25186177), thus providing direction for therapy development of FGFR blockade in PCa. Because dovitinib was withdrawn from the clinic by Novartis, we seek to identify an alternative agent with activity against FGFR1 as a candidate for therapy development. With that goal, we tested the antitumor activity of a specific pan-FGFR TKI, JNJ-42756493 (JNJ) (Janssen Pharmaceutical Companies of JohnsonJ 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2870.