Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications

Jinxia Chen; Zhiyuan Xu; Can Hu; Shengjie Zhang; Mengli Zi; Li Yuan; Xiangdong Cheng

doi:10.3389/fonc.2023.1132319

Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications

Front Oncol. 2023 Mar 10:13:1132319. doi: 10.3389/fonc.2023.1132319. eCollection 2023.

Authors

Jinxia Chen¹, Zhiyuan Xu^{1

2

3}, Can Hu^{1

2

3}, Shengjie Zhang^{1

2

3}, Mengli Zi¹, Li Yuan^{1

2

3}, Xiangdong Cheng^{1

2

3}

Affiliations

¹ Department of Gastric Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
² Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
³ Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China.

Abstract

Cancers of the gastrointestinal (GI) tract greatly contribute to the global cancer burden and cancer-related death. Claudin-18.2(CLDN18.2), a transmembrane protein, is a major component of tight junctions and plays an important role in the maintenance of barrier function. Its characteristic widespread expression in tumour tissues and its exposed extracellular loops make it an ideal target for researchers to develop targeted strategies and immunotherapies for cancers of the GI tract. In the present review, we focus on the expression pattern of CLDN18.2 and its clinical significance in GI cancer. We also discuss the tumour-promoting and/or tumour-inhibiting functions of CLDN18.2, the mechanisms regulating its expression, and the current progress regarding the development of drugs targeting CLDN18.2 in clinical research.

Keywords: Claudin-18.2; antibody–drug conjugate (ADC); chimeric antigen receptor T (CAR-T); gastrointestinal (GI) tract; monoclonal antibody.

Publication types

Review

Grants and funding

This study was supported by National Natural Sciences Foundation of China (82074245, 81973634), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Chinese Postdoctoral Science Foundation (2022M713203), Program of Zhejiang Provincial TCM Sci-tech Plan (2022ZQ020), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006).