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Casolino et al. Hepatoma Res 2021;7:76 Hepatoma Research
DOI: 10.20517/2394-5079.2021.79

Review Open Access

Treatment of advanced biliary tract cancers: from

chemotherapy to targeted agents

1,2
Raffaella Casolino , Chiara Braconi 1,3
1
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
2
Department of Medicine, University of Verona, Verona 37100, Italy.
3
Department of Medical Oncology, Beatson West Of Scotland Cancer Centre, Glasgow G12 0YN, UK.
Correspondence to: Dr. Chiara Braconi, Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of
Glasgow, Switchback Road, Glasgow G61 1QH, UK. E-mail: chiara.braconi@glasgow.ac.uk
How to cite this article: Casolino R, Braconi C. Treatment of advanced biliary tract cancers: from chemotherapy to targeted
agents. Hepatoma Res 2021;7:76. https://dx.doi.org/10.20517/2394-5079.2021.79
Received: 15 Jun 2021 First Decision: 6 Sep 2021 Revised: 8 Oct 2021 Accepted: 30 Oct 2021 Published: 5 Dec 2021

Academic Editor: Luca Aldrighetti Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage and have a dismal prognosis. The
treatment of advanced disease is mainly based on systemic chemotherapy, which is demonstrated to improve
survival in the first- and second-line setting. Following the results of phase III clinical trials, the combination of
cisplatin and gemcitabine is the regimen of choice in the frontline, while 5-fluorouracil plus oxaliplatin is considered
the standard after first-line progression in unselected patients. Recent advances in molecular biology have
unravelled the molecular heterogeneity of BTCs and identified patient subgroups harbouring unique molecular
aberrations such as isocitrate dehydrogenase (IDH) mutations and fibroblast growth factor receptor (FGFR)
fusions that can be targeted by specific agents. This knowledge has opened the way to personalised medicine in
BTCs. Molecules targeting IDH and FGFR are currently approved for the treatment of advanced, refractory,
intrahepatic cholangiocarcinoma. Beyond targeted therapies, novel combinatorial approaches that target the
immune microenvironment and the crosstalk between cancer and stroma are being explored based on strong
preclinical rationale. This review discusses the current therapeutic opportunities for the management of patients
with advanced BTCs and provides an overview of the promising new strategies on the horizon with a particular
focus on ongoing clinical trials.

Keywords: Biliary tract cancers, cholangiocarcinoma, precision medicine, targeted therapies, fibroblast growth
factor receptor, isocitrate dehydrogenase, chemotherapy

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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