Page 149 - Read Online

Yang et al. Hepatoma Res 2023;9:48 Hepatoma Research
DOI: 10.20517/2394-5079.2023.68

Review Open Access

Targeted mutation-based therapy for intrahepatic

cholangiocarcinoma

1,#
Facai Yang 1,2,# , Yinghe Qiu , Bin Yi 1
1
Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital, Biliary Tract Cancer Center, Naval Medical
University, Shanghai 201805, China.
2
Hepato-pancreato-biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
#
Authors contributed equally.
Correspondence to: Dr. Bin Yi, Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital; Biliary Tract
Cancer Center, Naval Medical University, No. 700 Moyubei Road, Jiading District, Shanghai 201805, China. E-mail:
billyyi11@163.com

How to cite this article: Yang F, Qiu Y, Yi B. Targeted mutation-based therapy for intrahepatic cholangiocarcinoma. Hepatoma
Res 2023;9:48. https://dx.doi.org/10.20517/2394-5079.2023.68

Received: 16 Jun 2023 First Decision: 25 Sep 2023 Revised: 24 Oct 2023 Accepted: 10 Nov 2023 Published: 16 Nov 2023

Academic Editors: Matias A Avila, Hongping Xia, Salvatore Gruttadauria Copy Editor: Dan Zhang Production Editor: Dan
Zhang

Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive primary liver cancer with limited treatment options
and poor prognosis. Although gemcitabine combined with cisplatin (GEMCIS) or newly GEMCIS plus durvalumab
is the first-line systemic therapy for iCCA, several promising treatment targets have been identified in the past
decade in both first- and subsequent-line settings, including neurotrophic tropomyosin-receptor tyrosine kinase
(NTRK) fusions, RET fusions, high microsatellite instability (MSI-H), high tumor mutation burden (TMB-H), as well
as fibroblast growth factor receptor 2 (FGFR2) fusions, BRAF V600E mutation, isocitrate dehydrogenase (IDH)-1
and IDH-2 mutations, and human epidermal growth factor receptor 2 [HER2 (ERBB2)] amplifications.
Corresponding small molecule inhibitors and monoclonal antibodies have demonstrated improved efficacy and
survival benefits in phase 2 or phase 3 studies, gained regulatory approvals or recommendations in guidelines, and
reshaped the therapeutic management for advanced cholangiocarcinoma. Numerous novel targeted drugs and
combination therapies have been developed and are under evaluation. Despite the progress made in targeted
therapy, it still faces challenges such as acquired drug resistance, precise patient selection, and serious adverse
events. Therefore, large-scale randomized phase 3 trials of novel targeted agents and innovative regimens are
warranted to benefit this population. Herein, we present a comprehensive review of the literature of clinical
significance on targeted therapy for iCCA in recent years, focusing on the advances in mutation-based targeted
therapy.

Keywords: Intrahepatic cholangiocarcinoma, genomic alterations, genetic landscape, targeted therapy

© The Author(s) 2023. 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.

www.oaepublish.com/hr