Resistance mechanism to fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma.

Abstract

Precision medicine is a major achievement that has impacted on management of patients diagnosed with advanced cholangiocarcinoma (CCA) over the last decade. Molecular profiling of CCA has identified targetable alterations, such as fibroblast growth factor receptor-2 (FGFR-2) fusions, and has thus led to the development of a wide spectrum of compounds. Despite favourable response rates, especially with the latest generation FGFRi, there are still a proportion of patients who will not achieve a radiological response to treatment, or who will have disease progression as the best response. In addition, for patients who do respond to treatment, secondary resistance frequently develops and mechanisms of such resistance are not fully understood. This review will summarise the current state of development of FGFR inhibitors in CCA, their mechanism of action, activity, and the hypothesised mechanisms of resistance.

• Authors: Angela Lamarca, Lorena Ostios, Mairéad G McNamara, Carlos Garzon, Jack P Gleeson, Julien Edeline, Ana Herrero, Richard A Hubner, Victor Moreno, Juan W Valle
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 121 Pg. 102627 (Dec 2023) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 37925878 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Fibroblast Growth Factor
• Receptor, Fibroblast Growth Factor, Type 2
• Protein Kinase Inhibitors

Topics

• Humans
• Receptors, Fibroblast Growth Factor
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)
• Cholangiocarcinoma (drug therapy, metabolism)
• Protein Kinase Inhibitors (adverse effects)
• Disease Progression
• Bile Ducts, Intrahepatic (metabolism, pathology)
• Bile Duct Neoplasms (drug therapy, pathology)