Ezh2 As a Potential Therapeutic Target for Gastrointestinal Cancers Publisher Pubmed



Hashemi M^{1, 2} ; Nazdari N² ; Gholamiyan G² ; Paskeh MDA^{1, 2} ; Jafari AM² ; Nemati F² ; Khodaei E³ ; Abyari G² ; Behdadfar N⁴ ; Raei B² ; Raesi R^{5, 6} ; Nabavi N⁷ ; Hu P⁸ ; Rashidi M^{9, 10} Show All Authors Show Affiliations
Source: Pathology Research and Practice Published:2024

Abstract

Gastrointestinal (GI) cancers continue to be a major cause of mortality and morbidity globally. Understanding the molecular pathways associated with cancer progression and severity is essential for creating effective cancer treatments. In cancer research, there is a notable emphasis on Enhancer of zeste homolog 2 (EZH2), a key player in gene expression influenced by its irregular expression and capacity to attach to promoters and alter methylation status. This review explores the impact of EZH2 signaling on various GI cancers, such as colorectal, gastric, pancreatic, hepatocellular, esophageal, and cholangiocarcinoma. The primary function of EZH2 signaling is to facilitate the accelerated progression of cancer cells. Additionally, EZH2 has the capacity to modulate the reaction of GI cancers to chemotherapy and radiotherapy. Numerous pathways, including long non-coding RNAs and microRNAs, serve as upstream regulators of EZH2 in these types of cancer. EZH2's enzymatic activity enables it to attach to target gene promoters, resulting in methylation that modifies their expression. EZH2 could be considered as an independent prognostic factor, with increased expression correlating with a worse disease prognosis. Additionally, a range of gene therapies including small interfering RNA, and anti-tumor agents are being explored to target EZH2 for cancer treatment. This comprehensive review underscores the current insights into EZH2 signaling in gastrointestinal cancers and examines the prospect of therapies targeting EZH2 to enhance patient outcomes. © 2023 Elsevier GmbH