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

Angela Lamarca, Lorena Ostios, Mairéad g Mcnamara, Carlos Garzon, Jack p Gleeson, Julien Edeline, Ana Herrero, Richard a Hubner, Victor Moreno, Juan w Valle

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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.
Original languageEnglish
Article number102627
JournalCancer Treatment Reviews
Early online date16 Sept 2023
DOIs
Publication statusE-pub ahead of print - 16 Sept 2023

Keywords

  • Cholangiocarcinoma
  • FGFR
  • Fusion
  • FGFR inhibitor
  • resistance
  • primary
  • secondary

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