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World J Gastroenterol. May 28, 2021; 27(20): 2507-2520
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2507
RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets
Shao-Long Chen, Guo-Ping Wang, Dan-Rong Shi, Shu-Hao Yao, Ke-Da Chen, Hang-Ping Yao
Shao-Long Chen, Ke-Da Chen, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310000, Zhejiang Province, China
Guo-Ping Wang, Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
Dan-Rong Shi, Hang-Ping Yao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Shu-Hao Yao, Department of Stomatology, Wenzhou Medical University Renji College, Wenzhou 325035, Zhejiang Province, China
Author contributions: Chen SL, Wang GP, Shi DR, Yao SH, Chen KD, and Yao HP discussed the necessity of writing this manuscript; Chen SL and Yao HP wrote the original draft; Chen SL, Wang GP, Shi DR, Yao SH, Chen KD, and Yao HP reviewed the draft with detailed comments; Chen SL and Yao HP made revisions to the manuscript; all authors read and approved the final manuscript for submission.
Supported by National Natural Sciences Foundation of China, No. 81872883; and Zhejiang Major Medical Health & Sciences Technology Foundation Projects, No. WKJ-ZJ-13.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hang-Ping Yao, PhD, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Shangcheng District, Hangzhou 310000, Zhejiang Province, China. yaohangping@zju.edu.cn
Received: December 31, 2020
Peer-review started: December 31, 2020
First decision: February 23, 2021
Revised: March 4, 2021
Accepted: April 9, 2021
Article in press: April 9, 2021
Published online: May 28, 2021
Abstract

The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family. Research has shown that RON has a role in cancer pathogenesis, which places RON on the frontline of the development of novel cancer therapeutic strategies. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death. Therefore, to combat these malignant diseases, the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis, and the development of RON as a drug target for therapeutic intervention should be investigated. Abnormal RON expression and signaling have been identified in HBP cancers, and also act as tumorigenic determinants for HBP cancer malignant behaviors. In addition, RON is emerging as an important mediator of the clinical prognosis of HBP cancers. Thus, not only is RON significant in HBP cancers, but also RON-targeted therapeutics could be developed to treat these cancers, for example, therapeutic monoclonal antibodies and small-molecule inhibitors. Among them, antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.

Keywords: RON, Signal transduction, Hepatobiliary, Pancreatic neoplasms, Molecular targeted therapy

Core Tip: The role of RON in cancer pathogenesis has received increasing research attention. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death because of their high rates of recurrence, metastasis, and invasiveness, and their lack of sensitivity to chemotherapy. In this review, we discuss how RON functions in HBP cancer pathogenesis, as well as its potential role as a therapeutic target in HBP cancers.