Abstract P31: FGFR Inhibitor, Erdafitinib, Reshapes Prostate Cancer Skeletal Metastases via Modulation of Cancer-Stemness and Tumor-Bone Interface
Agustina Sabater, Pablo Sanchis, Jun Yang, Peter D.A. Shepherd, Jiabin Dong, Elba Vazquez, Christopher Logothetis, Paul G. Corn, Geraldine Gueron, Estefania LabancaAbstract
Background:
Castration-resistant prostate cancer (CRPC) bone metastases lack curative therapies. Fibroblast growth factor receptor (FGFR) signaling is implicated in bone physiology, cancer stemness and therapy resistance. Previously, we demonstrated Dovitinib, a multi-tyrosine kinase inhibitor that targets FGFR, disrupts tumor-bone crosstalk. Here we evaluate Erdafitinib, a selective pan-FGFR inhibitor approved for metastatic urothelial carcinomas, for bone metastatic prostate cancer (PCa).
Methods:
Spheroid formation (area, circularity, solidity, Feret’s diameter) and cell viability were assessed in PCa (PC3, 22Rv1, C42b, DU145), osteoblast progenitor (MC3T3), FGFR1-overexpressing-PC3 and shFGFR1-MC3T3 cell lines treated with Erdafitinib. Tumor-free mice and mice intrafemorally grafted with PCa patient-derived xenografts (MDA-PCa-PDX) were treated (12.5mg/kg, BID 21 days). Tumor and non-tumor bearing femurs were analyzed via μCT and bone histomorphometry; tumors were monitored by MRI. A pilot clinical study evaluated Erdafitinib for CRPC bone metastases (NCT04754425).
Results:
Erdafitinib significantly disrupted PCa spheroids stem-like morphology. C42b were highly resistant, 22Rv1 and DU145 moderately responsive, and PC3 more sensitive (IC50 585.5nM), losing responsiveness with FGFR1-isoforms overexpression (α, 2508nM; β, 4896nM). MC3T3, pre-osteoblastic line, exhibited the highest sensitivity (49.75nM), independently of FGFR1 modulation. In tumor-free mice, Erdafitinib decreased bone volume, increased bone surface and modified trabecular architecture (number, thickness, separation, shape). In PDX-bearing mice, bone mineral density and volume were reduced in contralateral tumor-free and FGFR1-low tumor-bearing femurs. A 40% tumor volume reduction was observed in FGFR1-high tumors, without significant osseus changes. In our clinical study, 20% of patients responded to Erdafitinib with reductions in alkaline phosphatase levels but unchanged PSA, confirming bone-microenvironment targeting.
Conclusion:
Erdafitinib impacts PCa stem-like features and viability, with variable response. Importantly, it may disrupt the tumor-bone interplay by modulating both tumor stemness and the bone compartment, potentially posing a modified environment that may be less amenable for metastasis. Future directions will define responsive PCa patients and evaluate combinatorial strategies.
Citation Format:
Agustina Sabater, Pablo Sanchis, Jun Yang, Peter D.A. Shepherd, Jiabin Dong, Elba Vazquez, Christopher Logothetis, Paul G. Corn, Geraldine Gueron, Estefania Labanca. FGFR Inhibitor, Erdafitinib, Reshapes Prostate Cancer Skeletal Metastases via Modulation of Cancer-Stemness and Tumor-Bone Interface [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P31.