Therapeutic targeting of mismatch repair-deficient cancers



Summary

Mismatch repair deficient (dMMR) cancers, characterized by high microsatellite instability (MSI-H), represent a distinct subset with unique vulnerabilities. Lacking proper DNA repair mechanisms, they accumulate mutations, leading to neoantigen production and immune cell infiltration. This makes them highly susceptible to immunotherapy, particularly immune checkpoint inhibitors (ICIs) like pembrolizumab and nivolumab, which have demonstrated remarkable efficacy in these tumors. Furthermore, research explores novel therapeutic strategies targeting dMMR beyond ICIs, including DNA polymerase inhibitors and approaches aimed at exploiting the inherent replication stress caused by MMR deficiency. Understanding dMMR biology is crucial for personalized cancer treatment and expanding therapeutic options for these often aggressive malignancies.

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