Letter to the Editor
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2025; 31(11): 104065
Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.104065
Impact of poorly controlled type II diabetes mellitus on chemoresistance in colorectal cancer
Aditya Gaur, Rick Maity, Arkadeep Dhali, Jyotirmoy Biswas
Aditya Gaur, Foundation Training Program, Somerset NHS Foundation Trust, Yeovil BA20 2BX, Somerset, United Kingdom
Rick Maity, General Medicine, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India
Arkadeep Dhali, Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom
Arkadeep Dhali, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2HQ, United Kingdom
Arkadeep Dhali, Deanery of Clinical Sciences, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom
Arkadeep Dhali, School of Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom
Jyotirmoy Biswas, General Medicine, College of Medicine and Sagore Dutta Hospital, Kolkata 700058, India
Co-first authors: Aditya Gaur and Rick Maity.
Author contributions: Gaur A, Maity R, Dhali A, and Biswas J wrote the primary manuscript; Gaur A, Maity R, and Biswas J conducted literature review; Dhali A conceptualized the article; Gaur A and Maity R have contributed equally to the article and are co-first authors. All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arkadeep Dhali, MBBS, MPH, PGCert Clin Ed, FRSPH, NIHR Academic Clinical Fellow, Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. arkadipdhali@gmail.com
Received: December 9, 2024
Revised: January 16, 2025
Accepted: February 17, 2025
Published online: March 21, 2025
Processing time: 94 Days and 19.2 Hours
Abstract

Type 2 diabetes mellitus (T2DM) significantly elevates the risk of colorectal cancer (CRC) and complicates its treatment by promoting chemoresistance. Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy, impacting patient outcomes through various mechanisms such as oxidative stress, activation of metabolic pathways, and altered protein modifications that hinder apoptosis and enhance tumor survival. Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients. Specifically, those with poor glycemic control exhibit increased chemoresistance and poorer survival metrics. Antidiabetic treatments, including metformin, acarbose, and gliclazide, show promise in improving chemotherapy response and glycemic management, potentially enhancing patient outcomes. Addressing this challenge requires a comprehensive, multidisciplinary approach involving oncologists, endocrinologists, and surgeons to optimize patient care. Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.

Keywords: Type 2 diabetes mellitus; Colorectal cancer; Cancer; Chemoresistance; Diabetes mellitus; Hyperglycemia; Chemotherapy

Core Tip: Type 2 diabetes mellitus exacerbates colorectal cancer (CRC) progression by inducing chemoresistance through mechanisms such as oxidative stress, altered metabolic pathways, and disrupted apoptotic signalling. Poor glycemic control worsens patient outcomes, reducing disease-free survival and overall survival. Antidiabetic treatments, notably metformin, show potential in enhancing chemotherapy efficacy while improving glycemic management. A multidisciplinary care model involving oncologists, endocrinologists, and surgeons is essential to mitigate chemoresistance and optimize survival outcomes in CRC patients with type 2 diabetes mellitus. Prioritizing glycemic control through integrated therapeutic strategies offers a promising avenue for improving CRC treatment success in this high-risk patient population.