Rare cancer, rare alteration: the case of NTRK fusions in biliary tract cancers

Alice Boilève, Loïc Verlingue, Antoine Hollebecque, Valérie Boige, Michel Ducreux, David Malka

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Introduction: For patients with advanced/unresectable biliary tract cancers, cisplatin–gemcitabine combination is the standard first-line treatment. Beyond the first line, the therapeutic arsenal is limited with minimal benefit. Biliary tract cancers exhibit one of the highest frequencies of targetable molecular alterations across cancer types, and several targeted therapies are emerging as treatment options. Areas covered:We discuss neurotrophic tyrosine kinase receptor gene (NTRK) fusions in biliary tract cancers and the use of NTRK inhibitors (now approved in a ‘cancer-agnostic’ way), mechanisms of resistance, and emerging second-generation NTRK inhibitors. Expert opinion: Despite their rarity in biliary tract cancers, NTRK fusions are promising molecular targets because i) NTRK inhibitors have proven highly effective in NTRK-rearranged cancers and are now approved in a ‘cancer-agnostic’ way; ii) emerging second-generation NTRK inhibitors may overcome secondary resistance; iii) NTRK rearrangements will be readily detectable with the generalization of next-generation-sequencing in biliary tract cancers, including the detection of other frequent gene rearrangements, such as those involving the fibroblast growth factor receptor 2 gene (FGFR2). However, more data are necessary regarding the prevalence and characteristics of NTRK fusions in biliary tract cancers and the efficacy of NTRK inhibitors in these patients.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalExpert Opinion on Investigational Drugs
Volume30
Issue number4
DOIs
StatePublished - Apr 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Biliary tract cancer
  • NTRK fusions
  • entrectinib
  • investigational drugs
  • larotrectinib
  • precision medicine
  • precision oncology
  • rare cancers
  • tumor agnostic

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