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

Autor: Gilbert TM; 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., Randle L; Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK., Quinn M; Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK., McGreevy O; Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK., O'leary L; Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK., Young R; 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., Diaz-Neito R; Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK., Jones RP; 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., Greenhalf B; Liverpool Experimental Cancer Medicines Centre, University of Liverpool, Liverpool, UK., Goldring C; Department of Pharmacology and Therapeutics, Institute of Systems Integrative and Molecular Biology, University of Liverpool, Liverpool, UK., Fenwick S; Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK., Malik H; Hepatobiliary Surgery, Liverpool University Hospitals NHS FT, Liverpool, UK., Palmer DH; Clatterbridge Cancer Centre, Liverpool, UK; Liverpool Experimental Cancer Medicines Centre, University of Liverpool, Liverpool, UK.
Jazyk: angličtina
Zdroj: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology [Eur J Surg Oncol] 2024 Apr 17, pp. 108352. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1016/j.ejso.2024.108352
Abstrakt: 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.
Competing Interests: Declaration of competing interest Palmer has grant funding from BMS, Nucana, Astra Zeneca, Sirtex, honoraria from Boston Scientific and Sirtex, and support for travel from Nucana. Randle reports a relationship with National Centre for the Replacement Refinement and Reduction of Animals in Research (NC3Rs) that includes grant funding and membership of the NC3RS PhD studentship assessment board. Goldring reports financial support by the University of Liverpool. Jones, Young, Diaz-Neito, O’leary, McGreevy, Gilbert, Quinn, Fenwick and Malik declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 Published by Elsevier Ltd.)
Databáze: MEDLINE
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