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Faculty Perspectives: Clinical Relevance and Rationale of Using MSI-H/dMMR Biomarkers in Immunotherapy of Colorectal Cancer and Other Solid Tumors | Part 3 of a 4-Part Series

Faculty Perspectives: Clinical Relevance and Rationale of Using MSI-H/dMMR Biomarkers in Immunotherapy of Colorectal Cancer and Other Solid Tumors

There is renewed interest in MSI analysis because the MSI-H/dMMR phenotype has emerged as an actionable predictive biomarker for immune checkpoint blockade therapy in different cancer types. This review presents available evidence supporting the clinical relevance and predictive value of MSI/dMMR in cancers, including those treated with immune checkpoint inhibitors (ICIs), and outlines the diagnostic approaches developed to assess MSI/dMMR in clinical practice.
Genotyping tumors for microsatellite instability (MSI) has taken on new importance in the world of oncology. MSI screening has long been recognized as important in the care of patients with colorectal cancer (CRC) or endometrial cancer, and high-level MSI (MSI-H) is now being recognized as a potential marker for germline mutations in certain DNA mismatch-repair (MMR) genes that lead to the development of Lynch syndrome.
Studies examining the landscape of MSI in various cancers have shown that different tumor types tend to exhibit instability at different microsatellite loci throughout the genome, and a PCR-based test that is limited to the evaluation of only 5 loci may not adequately capture this heterogeneity.

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