Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2021; 13(9): 1073-1085
Published online Sep 15, 2021. doi: 10.4251/wjgo.v13.i9.1073
Potential utility of liquid biopsies in the management of patients with biliary tract cancers: A review
Rohan Shotton, Angela Lamarca, Juan Valle, Mairéad G McNamara
Rohan Shotton, Angela Lamarca, Juan Valle, Mairéad G McNamara, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
Angela Lamarca, Juan Valle, Mairéad G McNamara, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
Author contributions: Shotton R and McNamara MG designed the content of the manuscript, which was written by Shotton R (including the table and figure); all co-authors reviewed and approved the final version of the manuscript.
Conflict-of-interest statement: RS: Received travel and meeting funding from Servier; AL: Received travel and educational support from Ipsen, Pfizer, Bayer, AAA, Sirtex, Novartis, Mylan and Delcath. Speaker honoraria from Merck, Pfizer, Ipsen, and Incyte. Advisory honoraria from EISAI, Nutricia Ipsen, QED, and Roche. Member of the Knowledge Network and NETConnect Initiatives funded by Ipsen; JWV: Consulting or advisory role for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED, and Wren Laboratories; Speakers’ Bureau for Imaging Equipment Limited, Ipsen, Novartis, Nucana; and received Travel Grants from Celgene and Nucana; MMN: Received research grant support from Servier, Ipsen, and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana, and Mylan. She has served on advisory boards for Incyte, Celgene, Ipsen, Sirtex, and Baxalta.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Mairéad G McNamara, MBChB, PhD, Senior Lecturer, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.
Received: February 16, 2021
Peer-review started: February 16, 2021
First decision: May 3, 2021
Revised: June 14, 2021
Accepted: August 11, 2021
Article in press: August 11, 2021
Published online: September 15, 2021

Biliary tract cancer, comprising gallbladder cancer, cholangiocarcinoma and ampullary cancer, represents a more uncommon entity outside high-endemic areas, though global incidence is rising. The majority of patients present at a late stage, and 5-year survival remains poor. Advanced stage disease is incurable, and though palliative chemotherapy has been shown to improve survival, further diagnostic and therapeutic options are required in order to improve patient outcomes. Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations, attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness. Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic, predictive and prognostic biomarkers. In this review, the current standard of care for patients with biliary tract cancer, future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed. Circulating tumour DNA, circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer. A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.

Keywords: Biliary tract cancer, Liquid biopsy, Circulating tumour DNA, Cell free DNA, Circulating tumour cells, Biomarkers

Core Tip: Liquid biopsies represent an enticing prospect in biliary tract cancer. In this review, we discuss the rationale, methods and utility of liquid biopsies for predictive and prognostic purposes, including circulating tumour DNA, circulating tumour cells and circulating microRNA. A summary is provided of current trials utilising liquid biopsies in biliary tract cancer.