Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion–Positive Cholangiocarcinoma
Massachusetts General Hospital · Center for Cancer Research · +9 more institutions
Abstract
Abstract Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion–positive ICC in a phase II trial, but the durability of response was limited in some patients. Here, we report the molecular basis for acquired resistance to BGJ398 in three patients via integrative genomic characterization of cell-free circulating tumor DNA (cfDNA), primary tumors, and metastases. Serial analysis of cfDNA demonstrated multiple recurrent point mutations in the FGFR2 kinase domain at progression. Accordingly, biopsy of…
Citation impact
- FWCI
- 35.38
- Percentile
- 100%
- References
- 48
Authors
32- LGLipika Goyal
Massachusetts General Hospital, Center for Cancer Research
- SKSupriya K. Saha
Massachusetts General Hospital, Center for Cancer Research
- LYLeah Y. Liu
Massachusetts General Hospital, Center for Cancer Research
- GSGiulia Siravegna
5T Torino (Italy), IFOM, Italian Association for Cancer Research, Torino e-district, Candiolo Cancer Institute, University of Turin
- ILIgnaty Leshchiner
Broad Institute, Massachusetts Institute of Technology
Topics & keywords
- Fibroblast growth factor receptor
- Cancer research
- Mutation
- Point mutation
- Biology
- Cancer
- Targeted therapy
- Fibroblast growth factor receptor 2
- Good health and well-being