Targeting minimal residual disease (MRD) in colorectal cancer: Therapeutic strategies, clinical trials, and the path toward molecular cure
6 affiliations
- 1Department of Anatomy, College of Medicine, University of Ha'il, Ha'il 55473, Saudi Arabia
- 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Aljouf 72388, Saudi Arabia
- 3Department of Family and Community Medicine, College of Medicine, University of Ha'il, Ha'il 55473, Saudi Arabia
- 4Department of Surgery, College of Medicine, University of Ha'il, Ha'il 55473, Saudi Arabia
- 5Department of Biochemistry, College of Medicine, University of Ha'il, Ha'il 55473, Saudi Arabia
- 6Department of Pharmacology, College of Medicine, University of Ha'il, Ha'il 55473, Saudi Arabia
Abstract
The management of early-stage colorectal cancer (CRC) is undergoing a significant transformation, from traditional clinical and pathological staging to a dynamic, molecular signature-driven approach utilizing circulating tumor DNA (ctDNA). Postoperative detection of minimal residual disease (MRD) has emerged as a strong independent prognostic biomarker. It identifies patients at high risk of recurrence while reducing unnecessary exposure to adjuvant chemotherapy for those cured by surgery alone. However, this success reveals a critical therapeutic dilemma. Standard adjuvant chemotherapy has a limited ability to eliminate MRD. Consequently, the molecularly defined high-risk subgroup currently has no proven therapy that effectively eradicates MRD and improves survival. In this review, we synthesize emerging therapeutic strategies designed to address this unmet need. We discuss ongoing clinical trials investigating intensified cytotoxic regimens, MRD-guided targeted therapies, and novel immunotherapy combinations, especially for microsatellite-stable (MSS) disease. Furthermore, this review examines the role of ctDNA dynamics as a surrogate endpoint for regulatory drug approval, a crucial step in accelerating the development of these novel therapies. Finally, we address the real-world challenges of implementation, including access disparities, equity gaps, and standardized clinical algorithms. We highlight how emerging technologies and global collaborations may further refine MRD detection. The eradication of MRD represents the next frontier in curing CRC; however, this demands focused clinical research and validated surrogate endpoints to translate prognostic insights into tangible survival benefits.
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BibTeX
@article{khan2026targeting,
title = {{Targeting minimal residual disease (MRD) in colorectal cancer: Therapeutic strategies, clinical trials, and the path toward molecular cure}},
author = {Yusuf Saleem Khan and Aisha Farhana and Hatim Adam Nagi and Alfatih Mohamed Ahmed Alnajib and Tarig Ginawi and Abuzar Abdulwahab Osman and Abdullah Alsrhani and Emad Manni},
journal = {Cancer pathogenesis and therapy},
year = {2026},
month = jul,
doi = {10.1016/j.cpt.2026.07.003},
url = {https://europepmc.org/article/PMC/PMC13717014},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting minimal residual disease (MRD) in colorectal cancer: Therapeutic strategies, clinical trials, and the path toward molecular cure
AU - Yusuf Saleem Khan
AU - Aisha Farhana
AU - Hatim Adam Nagi
AU - Alfatih Mohamed Ahmed Alnajib
AU - Tarig Ginawi
AU - Abuzar Abdulwahab Osman
AU - Abdullah Alsrhani
AU - Emad Manni
PY - 2026
DA - 2026/07/23
JO - Cancer pathogenesis and therapy
DO - 10.1016/j.cpt.2026.07.003
UR - https://europepmc.org/article/PMC/PMC13717014
AB - The management of early-stage colorectal cancer (CRC) is undergoing a significant transformation, from traditional clinical and pathological staging to a dynamic, molecular signature-driven approach utilizing circulating tumor DNA (ctDNA). Postoperative detection of minimal residual disease (MRD) has emerged as a strong independent prognostic biomarker. It identifies patients at high risk of recurrence while reducing unnecessary exposure to adjuvant chemotherapy for those cured by surgery alone. However, this success reveals a critical therapeutic dilemma. Standard adjuvant chemotherapy has a limited ability to eliminate MRD. Consequently, the molecularly defined high-risk subgroup currently has no proven therapy that effectively eradicates MRD and improves survival. In this review, we synthesize emerging therapeutic strategies designed to address this unmet need. We discuss ongoing clinical trials investigating intensified cytotoxic regimens, MRD-guided targeted therapies, and novel immunotherapy combinations, especially for microsatellite-stable (MSS) disease. Furthermore, this review examines the role of ctDNA dynamics as a surrogate endpoint for regulatory drug approval, a crucial step in accelerating the development of these novel therapies. Finally, we address the real-world challenges of implementation, including access disparities, equity gaps, and standardized clinical algorithms. We highlight how emerging technologies and global collaborations may further refine MRD detection. The eradication of MRD represents the next frontier in curing CRC; however, this demands focused clinical research and validated surrogate endpoints to translate prognostic insights into tangible survival benefits.
SN - 2097-2563
SN - 2949-7132
ER -