Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 18, Issue 7, Pages 2821-2832Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.71714
Keywords
MMR; Development; Immunotherapy; DNA repair; Cancer
Categories
Funding
- Anhui Provincial Natural Science Foundation [2108085MH285]
- Fundamental Research Funds for the Central Universities [WK9110000154]
- Hunan Postdoctoral Program for Innovative Talent [2021RC2017]
- Natural Science Foundation of Hunan Province [2021JJ41027]
- China Postdoctoral Science Foundation [2021M693567, 2021TQ0374]
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DNA mismatch repair is a crucial pathway for maintaining genomic stability, and its deficiency can lead to microsatellite instability, affecting tumor growth. Immunotherapies targeting MMR can increase the burden of neoantigens in tumor cells and serve as predictors for sensitivity and drug resistance in immunotherapy.
DNA mismatch repair (MMR) is an important pathway which helps to maintain genomic stability. Mutations in DNA MMR genes are found to promote cancer initiation and foster tumor progression. Deficiency or inactivation of MMR results in microsatellite instability (MSI) which triggers neoantigen generation and impairs tumor growth. Immunotherapies targeting MMR can increase the burden of neoantigens in tumor cells. While MSI has been regarded as an important predictor of sensitivity and drug resistance for immunotherapy-based strategies. Different approaches targeting genomic instability have been demonstrated to be promising in malignancies derived from different tissues. Underlying MMR deficiency-associated immunogenicity is important for improving the therapeutic efficacy of immunotherapies. In this review we provide an overview of the MMR systems, their role in tumorigenesis, drug resistance, prognostic significance and potential targets for therapeutic treatment in human cancers, especially in hematological malignancies.
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