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Editorial
. 2023 Oct 1;12(5):790-794.
doi: 10.21037/hbsn-23-411. Epub 2023 Sep 15.

The role of FGFR inhibitors in the treatment of intrahepatic cholangiocarcinoma-unveiling the future challenges in drug therapy

Naoshi Nishida  1
Affiliations
Editorial

The role of FGFR inhibitors in the treatment of intrahepatic cholangiocarcinoma-unveiling the future challenges in drug therapy

Naoshi Nishida. Hepatobiliary Surg Nutr. .
No abstract available

Keywords: Intrahepatic cholangiocarcinoma (iCCA); chemotherapy; fibroblast growth factor receptor inhibitor (FGFR inhibitor); mutation; tumor immune microenvironment (TIME).

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Conflict of interest statement

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-411/coif). The author reports that this work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI: 21K07184), and a grant from Smoking Research Foundation.

Figures

Figure 1
Figure 1
Attenuation of inhibitory effect of FGFR inhibitors against resistant mutation within the kinase domain of FGFR2. Attenuation of inhibitory effects are shown as a ratio of half-maximum inhibitory concentrations (IC50) on mutant FGFR2 to those on wild type. Several mutations emerged in the kinase domain of FGFR2 result in the resistant to reversible ATP-competitive FGFR inhibitors with IC50 ratio of ≥10. On the other hand, only one mutation, V565L, induces the resistance against the irreversible FGFR1-4 inhibitor with IC50 ratio of ≥10. The graph was drawn based on the data from (9), Figure 1 and (11). Futibatinib, irreversible FGFR1-4 inhibitor. Pemigatinib, reversible FGFR1-3 inhibitor. Infigratinib, reversible FGFR1-3 inhibitor. Erdafitinib, reversible FGFR1-4 inhibitor. FGFR, fibroblast growth factor receptor; ATP, adenosine triphosphate.
Figure 2
Figure 2
Illustration of proposed hypothesis on induction of non-inflamed tumor by FGFR2 fusion/rearrangement. Aberrant FGFR2, such as fusion and rearrangement, induce activation of FGF signaling that lead to the induction of the SOCS1. This, in turn, hampers the upregulation of HLA through the interferon-γ pathway, potentially perpetuating the “non-inflamed” tumor state because of loss of antigen presentation machineries. HLA, human leukocyte antigen; FGF, fibroblast growth factor; SOCS1, suppressor of cytokine signaling 1; FGFR2, fibroblast growth factor receptor 2; BICC1, BicC family RNA binding protein 1.
See this image and copyright information in PMC

Comment on

  • Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma.
    Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klümpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Goyal L, et al. N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834. N Engl J Med. 2023. PMID: 36652354 Clinical Trial.

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