Pan-FGFR inhibitors, targeting FGFR1-3 or FGFR1-4, are FDA-approved for FGFR2-driven cholangiocarcinoma. However, acquired resistance and dose-limiting toxicities from systemic FGFR inhibition constrain efficacy. Lirafugratinib (RLY-4008), a first-in-class FGFR2-selective inhibitor with activity against resistance-associated FGFR2 kinase domain mutations, shows promise in patients with FGFR2-altered solid tumors (ReFocus trial, NCT04526106). Defining acquired resistance mechanisms to selective FGFR2 targeting is essential for therapeutic…
Mechanisms of Clinical Resistance to Selective FGFR2 Inhibition by Lirafugratinib
Annals of Oncology | | H. Ellis, E.R. Balasooriya, A. Varkaris, B. Hajian, J. Wan, M. Shekhar, I. Gritti, V. Vijay, L. Albertelli, S. Piot, K. Lau, A. Kehlmann, N. Chevalier, F.W. Nugent, Y. Zhen, V.S. Silveira, W.R. Sellers, R.B. Corcoran, D. Juric, N. Bardeesy
Topics: liver-cancer, cervical-cancer, breakthrough-drugs, research