| Autor: |
Funda Meric-Bernstam, Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt Evans, Erkan Yuca, Stephen Scott, Bryce Kirby, Xiaofeng Zheng, Min Jin Ha, Huiqin Chen, Patrick Ng, Tiimothy DiPeri, Gordon Mills, Jordi Rodon, Senthil Damodaran |
| Rok vydání: |
2022 |
| Popis: |
The role of the fibroblast growth factor receptor (FGFR) gene alterations as therapeutic targets in breast cancer have not been well characterized. Futibatinib (TAS-120; Taiho) is a novel pan-FGFR inhibitor. We sought to determine the efficacy of futibatinib in breast cancer models with FGFR alterations. Nine breast cancer patient–derived xenografts (PDXs) with a variety of FGFR1-4 alterations and expression levels were treated with futibatinib. FGFR gene expression between patient tumors and matching PDXs was significantly correlated. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1–2.6% and 1.5–2.5%, respectively. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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