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Review
. 2023 Apr 13;15(8):2288.
doi: 10.3390/cancers15082288.

Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy

Alexandra Kavun  1 , Egor Veselovsky  1   2 , Alexandra Lebedeva  1 , Ekaterina Belova  1   3 , Olesya Kuznetsova  1   4 , Valentina Yakushina  1   5 , Tatiana Grigoreva  1   6 , Vladislav Mileyko  1 , Mikhail Fedyanin  4   7   8 , Maxim Ivanov  1   9
Affiliations
Review

Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy

Alexandra Kavun et al. Cancers (Basel). .

Abstract

Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome. Additionally, we summarize the results of major clinical studies on the efficacy of immune checkpoint inhibitors for MSI tumors and discuss the predictive role of MSI in the context of chemotherapy and checkpoint inhibitors. Finally, we briefly discuss some of the underlying mechanisms causing therapy resistance in patients treated with immune checkpoint inhibitors.

Keywords: biomarker; immune checkpoint inhibitors; microsatellite instability; mismatch repair; precision medicine.

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Conflict of interest statement

A.K., E.V., A.L., E.B., O.K., V.Y., T.G., V.M., M.F are employees of OncoAtlas LLC. Other co-authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Lynch syndrome-associated cancer risks by age 80, according to the NCCN guidelines. GP = general population.
Figure 2
Figure 2
The landscape of MSI and genomic characteristics of MSI tumors across cancer types, according to TCGA. (A) Prevalence of MSI (%) across tumor types. (B) Prevalence of genomic alterations typically found in MSI and MSS tumors in colorectal adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma.
Figure 3
Figure 3
FDA approval timeline of immune checkpoint inhibitors for MSI/dMMR tumors.
See this image and copyright information in PMC

References

    1. Baretti M., Le D.T. DNA Mismatch Repair in Cancer. Pharmacol. Ther. 2018;189:45–62. doi: 10.1016/j.pharmthera.2018.04.004. - DOI - PubMed
    1. Ma J., Setton J., Lee N.Y., Riaz N., Powell S.N. The Therapeutic Significance of Mutational Signatures from DNA Repair Deficiency in Cancer. Nat. Commun. 2018;9:3292. doi: 10.1038/s41467-018-05228-y. - DOI - PMC - PubMed
    1. Bass A.J., Thorsson V., Shmulevich I., Reynolds S.M., Miller M., Bernard B., Hinoue T., Laird P.W., Curtis C., Shen H., et al. Comprehensive Molecular Characterization of Gastric Adenocarcinoma. Nature. 2014;513:202–209. doi: 10.1038/NATURE13480. - DOI - PMC - PubMed
    1. Lepore Signorile M., Disciglio V., di Carlo G., Pisani A., Simone C., Ingravallo G. From Genetics to Histomolecular Characterization: An Insight into Colorectal Carcinogenesis in Lynch Syndrome. Int. J. Mol. Sci. 2021;22:6767. doi: 10.3390/ijms22136767. - DOI - PMC - PubMed
    1. Lower S.S., McGurk M.P., Clark A.G., Barbash D.A. Satellite DNA Evolution: Old Ideas, New Approaches. Curr. Opin. Genet. Dev. 2018;49:70–78. doi: 10.1016/j.gde.2018.03.003. - DOI - PMC - PubMed

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