Mulet Margalef, NúriaLinares Aceituno, Jenniffer LissetheBadia-Ramentol, JordiJimeno, MireyaSanz Monte, CarolinaManzano Mozo, José LuisCalon, Alexandre2024-04-172024-04-172023Mulet-Margalef N, Linares J, Badia-Ramentol J, Jimeno M, Sanz Monte C, Manzano Mozo JL, et al. Challenges and Therapeutic Opportunities in the dMMR/MSI-H Colorectal Cancer Landscape. Cancers (Basel). 2023 Feb 6;15(4):1022. DOI: 10.3390/cancers150410222072-6694http://hdl.handle.net/10230/59800About 5 to 15% of all colorectal cancers harbor mismatch repair deficient/microsatellite instability–high status (dMMR/MSI-H) that associates with high tumor mutation burden and increased immunogenicity. As a result, and in contrast to other colorectal cancer phenotypes, a significant subset of dMMR/MSI-H cancer patients strongly benefit from immunotherapy. Yet, a large proportion of these tumors remain unresponsive to any immuno-modulating treatment. For this reason, current efforts are focused on the characterization of resistance mechanisms and the identification of predictive biomarkers to guide therapeutic decision-making. Here, we provide an overview on the new advances related to the diagnosis and definition of dMMR/MSI-H status and focus on the distinct clinical, functional, and molecular cues that associate with dMMR/MSI-H colorectal cancer. We review the development of novel predictive factors of response or resistance to immunotherapy and their potential application in the clinical setting. Finally, we discuss current and emerging strategies applied to the treatment of localized and metastatic dMMR/MSI-H colorectal tumors in the neoadjuvant and adjuvant setting.application/pdfeng© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/cancers15041022Colorectal cancerMismatch repairMicrosatellite instabilityImmunotherapyinfo:eu-repo/semantics/openAccess