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Ruff et al. Hepatoma Res 2023;9:37 Hepatoma Research
DOI: 10.20517/2394-5079.2023.51

Review Open Access

Review of IDH mutations and potential therapies for

intrahepatic cholangiocarcinoma

Samantha M. Ruff, Mary Dillhoff
Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James
Comprehensive Cancer Center, Columbus, OH 43210, USA.

Correspondence to: Prof. Mary Dillhoff, MD, Department of Surgical Oncology, The Ohio State University Wexner Medical
Center and James Comprehensive Cancer Center, 320 W. 10th Ave, M-256 Starling Loving Hall, Columbus, OH 43210, USA. E-
mail: mary.dillhoff@osumc.edu
How to cite this article: Ruff SM, Dillhoff M. Review of IDH mutations and potential therapies for intrahepatic
cholangiocarcinoma. Hepatoma Res 2023;9:37. https://dx.doi.org/10.20517/2394-5079.2023.51
Received: 23 May 2023 First Decision: 4 Jul 2023 Revised: 17 Jul 2023 Accepted: 28 Jul 2023 Published: 3 Aug 2023

Academic Editor: Feng Shen Copy Editor: Dan Zhang Production Editor: Dan Zhang

Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy that arises from the biliary tract. Currently, the first-line
therapy for advanced CCA is gemcitabine and cisplatin. However, 5-year survival remains low. It has become
abundantly clear that a “one size fits all” approach no longer applies to the treatment of individual cancers, given
the large amount of tumor heterogeneity. As such, research in recent years has focused on developing effective
targeted therapies through genetic profiling of CCA tumors. IDH1 and IDH2 mutations are commonly found in
intrahepatic CCA (ICCA). IDH mutations prevent hepatic progenitor cell differentiation and result in the
persistence of progenitor-like and stem cells. These are more prone to alterations that promote tumor initiation. As
such, IDH has been identified as a promising target for ICCA treatment. We herein review the role of IDH
mutations in ICCA development, recent data for IDH inhibitors in ICCA treatment, and challenges within the field
of targeted therapy for ICCA.

Keywords: Intrahepatic cholangiocarcinoma, IDH, targeted therapy, ivosidenib, mechanisms of resistance

INTRODUCTION
Cholangiocarcinoma (CCA) is a rare and aggressive malignancy that originates from the biliary tract. It can
be divided anatomically into intrahepatic and extrahepatic (hilar and distal) CCA. Intrahepatic CCA

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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