Journal Article Review Epublish
PubMed: 40649818 DOI: 10.3390/ijms26136040
Metformin in Colorectal Cancer: Epidemiological Evidence, Predictive Biomarkers, and Implications for Prevention and Treatment.
Int J Mol Sci 26(13)
Authors: Seokho Myung, Youn Young Park, Man S Kim
Affiliations
- Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea. Department of Medicine, Kyung Hee University College of Medicine, Seoul 02453, Republic of Korea.
- Department of Medicine, Kyung Hee University College of Medicine, Seoul 02453, Republic of Korea. Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea.
Abstract
Interest in metformin as a potential anticancer agent for colorectal cancer (CRC) has increased. However, compelling epidemiological links and strong preclinical evidence suggest that metformin has variable efficacy in patients with CRC. This variability highlights the need to identify the patients who are most likely to benefit from effective stratification. We aimed to review the evidence concerning the diverse roles of metformin in CRC prevention and treatment, focusing on identifying and validating the predictive biomarkers essential for selecting patient subgroups that are likely to respond positively. We explored the various molecular pathways through which metformin acts and investigated how these diverse mechanisms might explain the observed differences in patient responses. Epidemiological studies and large meta-analyses have consistently reported reduced CRC incidence and improved survival among patients with diabetes treated with metformin. However, successfully extending these benefits broadly across all patients with CRC or achieving predictable outcomes in advanced disease settings remains a significant challenge. This review consolidates the current knowledge, highlights how different mechanisms interact, critically assesses clinical evidence in light of patient heterogeneity, and advocates for the development and implementation of biomarker-guided personalized therapeutic strategies as key to optimally utilizing the potential of metformin in CRC management. The current challenges and vital future research priorities in this critical area are also outlined.
MeSH
Diabetes Mellitus, Neoplasms, Biomarkers, Precision Medicine, Therapeutics, Colorectal Neoplasms, Tumor Microenvironment, Metformin