Fgfr2, short for fibroblast growth factor receptor 2, is a key receptor in the fibroblast growth factor signaling pathway. This pathway is involved in numerous biological processes such as cell growth, differentiation, and angiogenesis. Alterations in Fgfr2 can have significant impacts on these normal cellular functions [1-10].

Somatic hotspot mutations, structural amplifications, and fusions of Fgfr2 occur in multiple cancer types. Transposon-based screening and tumour modelling in mice have shown that the truncation of exon 18 of Fgfr2 is a potent driver mutation [3]. In cholangiocarcinoma, FGFR2 fusions are present in 10-15% of intrahepatic cases, making it a promising target for precision oncology [1,4,6]. FGFR inhibitors like futibatinib, pemigatinib, and TAS-120 have demonstrated clinical benefit in patients with FGFR2-altered cholangiocarcinoma, but issues like acquired resistance and off-target toxicities remain challenges [2,5,6].

In conclusion, Fgfr2 is crucial in regulating cell-related biological processes through its signaling pathway. Mouse models have been instrumental in identifying its oncogenic mutations, especially in cholangiocarcinoma. Targeting Fgfr2 has shown potential in treating certain cancers, but further research is needed to overcome resistance and toxicity issues.

References:

1. Vogel, Arndt, Segatto, Oreste, Stenzinger, Albrecht, Saborowski, Anna. 2022. FGFR2 Inhibition in Cholangiocarcinoma. In Annual review of medicine, 74, 293-306. doi:10.1146/annurev-med-042921-024707. https://pubmed.ncbi.nlm.nih.gov/36170665/

2. Goyal, Lipika, Meric-Bernstam, Funda, Hollebecque, Antoine, Benhadji, Karim A, Bridgewater, John A. . Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. In The New England journal of medicine, 388, 228-239. doi:10.1056/NEJMoa2206834. https://pubmed.ncbi.nlm.nih.gov/36652354/

3. Zingg, Daniel, Bhin, Jinhyuk, Yemelyanenko, Julia, Wessels, Lodewyk F A, Jonkers, Jos. 2022. Truncated FGFR2 is a clinically actionable oncogene in multiple cancers. In Nature, 608, 609-617. doi:10.1038/s41586-022-05066-5. https://pubmed.ncbi.nlm.nih.gov/35948633/

4. Angerilli, Valentina, Fornaro, Lorenzo, Pepe, Francesco, Malapelle, Umberto, Fassan, Matteo. 2023. FGFR2 testing in cholangiocarcinoma: translating molecular studies into clinical practice. In Pathologica, 115, 71-82. doi:10.32074/1591-951X-859. https://pubmed.ncbi.nlm.nih.gov/37017301/

5. Goyal, Lipika, Shi, Lei, Liu, Leah Y, Corcoran, Ryan B, Bardeesy, Nabeel. 2019. TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma. In Cancer discovery, 9, 1064-1079. doi:10.1158/2159-8290.CD-19-0182. https://pubmed.ncbi.nlm.nih.gov/31109923/

6. Storandt, Michael H, Jin, Zhaohui, Mahipal, Amit. 2022. Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion. In Expert review of anticancer therapy, 22, 1265-1274. doi:10.1080/14737140.2022.2150168. https://pubmed.ncbi.nlm.nih.gov/36408971/