Defective DNA Mismatch Repair as a Biomarker in Cancer Diagnosis and Immunotherapy: Review Article

The DNA mismatch repair (MMR) system is essential for maintaining genomic integrity by correcting base–base mismatches and insertion–deletion loops generated during DNA replication. Defects in this pathway result in microsatellite instability (MSI) and a hypermutated tumor phenotype with profound biological and clinical consequences. Over the past decade, deficient mismatch repair (dMMR) and MSI-high (MSI-H) status have emerged as robust biomarkers for cancer screening, molecular diagnosis, prognostic stratification, and prediction of response to immune checkpoint blockade (ICB). This narrative review summarizes the molecular biology of the MMR system, mechanisms leading to MMR deficiency, current diagnostic strategies for MSI/MMR assessment, and the pivotal role of dMMR as a predictive biomarker for immunotherapy across multiple cancer types. Emphasis is placed on clinical applications, limitations, and emerging directions in precision oncology.