Abstract 6840: FGFR cell lines: A comprehensive approach to drug discovery and evaluation, from small molecules to biologics, covering binding to activation

Abstract Fibroblast growth factors (FGFs) bind to their receptors (fibroblast growth factor receptors, FGFRs), activating downstream signaling pathways, which play crucial roles in both mitogenic processes, such as embryogenesis and growth, and non-mitogenic processes, such as neuroregulation and metabolic regulation. FGFRs primarily consist of four subtypes: FGFR1, FGFR2, FGFR3, and FGFR4. Abnormalities like high expression or mutations in these receptors can lead to the aberrant activation of their signaling pathways, resulting in tumorigenesis. Consequently, targeting FGFR is a promising strategy for cancer therapy. Current FGFR-targeting drugs, either in clinical use or under development, include small molecule inhibitors, antibodies, antibody-drug conjugates (ADCs), CAR-T therapies, and soluble FGFR receptors. Different cell models are required for efficacy evaluation of various drug types. Kyinno has developed a comprehensive series of FGFR-related cell lines, which include Ba/F3 kinase cells, FGFR overexpression cells, knockout cells, and reporter cells. Among these, Ba/F3 cells have been meticulously engineered to depend on various FGFR point mutations and fusion mutations for survival, showcasing robust capabilities in evaluating FGFR small molecule inhibitors. The FGFR overexpression and knockout cells are crucial for assessing antibody binding, ADC drug endocytosis, and certain radioimmuno conjugates (RICs). Reporter cells, designed based on FGFR downstream signaling pathways, cover a spectrum of wild-type and point-mutated FGFR subtypes, thus effectively evaluating the impact of drugs on downstream signaling pathways. This strategic array of cell models collectively enhances the development and validation of FGFR-targeted therapies, providing invaluable insights and tools for advancing cancer treatment research. By leveraging these diverse cell models, researchers can better understand the mechanisms of FGFR-targeted interventions, ultimately contributing to more effective therapeutic strategies. Citation Format: Siyu Li, Yao Peng, Yu Wang, Maimaitiming Nuermanguli, Jinying Ning, Feng Hao. FGFR cell lines: A comprehensive approach to drug discovery and evaluation, from small molecules to biologics, covering binding to activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6840.