Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastroenterol. May 7, 2026; 32(17): 118502
Published online May 7, 2026. doi: 10.3748/wjg.v32.i17.118502
Published online May 7, 2026. doi: 10.3748/wjg.v32.i17.118502
Epigenetic landscape of gastrointestinal stromal tumors: Mechanistic insights and therapeutic opportunities
Stavros P Papadakos, First Academic Department of Gastroenterology, National and Kapo
Stavros P Papadakos, Georgios Mandrakis, Hara Gakiopoulou, Stamatios Theocharis, First Department of Pathology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens 11527, Greece
Spyros I Siakavellas, Second Academic Department of Internal Medicine, Liver-GI Unit, General Hospital of Athens “Hippocration”, National and Kapodistrian University of Athens, Athens 11527, Greece
Nikolaos Memos, First Department of Propaedeutic Surgery, “Hippokratio” General Hospital, Medical School of Athens National and Kapodistrian University of Athens, Athens 11527, Greece
Dimitrios Schizas, First Department of Surgery, National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens 11527, Greece
Co-corresponding authors: Stavros P Papadakos and Stamatios Theocharis.
Author contributions: Papadakos SP and Theocharis S contributed to conceptualization; Papadakos SP and Mandrakis G contributed to data curation; Papadakos SP, Mandrakis G and Siakavellas SI contributed to investigation; Papadakos SP contributed to methodology and writing original draft; Memos N contributed to validation and clinical interpretation; Gakiopoulou H, Schizas D and Theocharis S contributed to supervision; all authors contributed to writing, review and editing.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Stavros P Papadakos, MD, Doctor, First Academic Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Agiou Thoma 17, Athens 11527, Greece. stavrospapadakos@gmail.com
Received: January 4, 2026
Revised: January 29, 2026
Accepted: February 13, 2026
Published online: May 7, 2026
Processing time: 110 Days and 18.2 Hours
Revised: January 29, 2026
Accepted: February 13, 2026
Published online: May 7, 2026
Processing time: 110 Days and 18.2 Hours
Core Tip
Core Tip: Gastrointestinal stromal tumors (GISTs) are driven primarily by KIT or PDGFRA mutations, yet therapeutic resistance and heterogeneous clinical behavior remain major challenges. This review highlights how epigenetic mechanisms DNA methylation, histone modifications, and chromatin remodeling shape GIST initiation, progression, and treatment response. We synthesize preclinical and clinical evidence linking epigenetic alterations to prognosis, resistance, and emerging therapeutic vulnerabilities, and discuss how chromatin-directed strategies may complement tyrosine kinase inhibition to advance precision oncology in GIST.