Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management

T M Gilbert; L Randle; M Quinn; O McGreevy; L O'leary; R Young; R Diaz-Neito; R P Jones; B Greenhalf; C Goldring; S Fenwick; H Malik; D H Palmer

doi:10.1016/j.ejso.2024.108352

Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management

Eur J Surg Oncol. 2024 Apr 17:108352. doi: 10.1016/j.ejso.2024.108352. Online ahead of print.

Authors

T M Gilbert¹, L Randle², M Quinn³, O McGreevy², L O'leary³, R Young⁴, R Diaz-Neito³, R P Jones⁴, B Greenhalf⁵, C Goldring², S Fenwick³, H Malik³, D H Palmer⁶

Affiliations

¹ Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK; Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK. Electronic address: timothy.gilbert@liverpool.ac.uk.
² Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK.
³ Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK.
⁴ Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK; Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK.
⁵ Liverpool Experimental Cancer Medicines Centre, University of Liverpool, Liverpool, UK.
⁶ Clatterbridge Cancer Centre, Liverpool, UK; Liverpool Experimental Cancer Medicines Centre, University of Liverpool, Liverpool, UK.

PMID: 38653586
DOI: 10.1016/j.ejso.2024.108352

Abstract

Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer. The identification of 'druggable' genetic aberrations and the development of novel targeted therapies against them is opening up new treatment strategies. Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. As our understanding of the biology underpinning CCA continues to improve it is highly likely that additional targeted therapies will become available in the near future. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.

Keywords: Cholangiocarcinoma; Molecular biology; Patient treatment; Targeted therapy.