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Review
. 2021 Feb 6;13(4):651.
doi: 10.3390/cancers13040651.

Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Mojun Zhu  1 , Zhaohui Jin  1 , Joleen M Hubbard  1
Affiliations
Review

Management of Non-Colorectal Digestive Cancers with Microsatellite Instability

Mojun Zhu et al. Cancers (Basel). .

Abstract

Microsatellite instability (MSI) is a hallmark of genetic predisposition to DNA damage. It arises from either germline or somatic events leading to impaired function of the mismatch repair system. It can be detected via genetic sequencing or immunohistochemistry with relatively high concordance rates. The presence of MSI in a tumor reflects a high neoantigen load and predicts favorable treatment response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI is a predictive biomarker for ICIs with potential prognostic impact but its clinical utility varies widely depending on tumor type. This may be explained by the complexity of tumor microenvironment as highlighted by recent translational studies. In this review, we will discuss the predictive and prognostic value of MSI status in non-colorectal cancers of the digestive system, important clinical trials involving ICIs and potential strategies to overcome resistance to immunotherapy.

Keywords: checkpoint; gastrointestinal cancer; microsatellite instability.

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Conflict of interest statement

M.Z. and Z.J. declare no conflict of interest. J.M.H. receives research funding for the Mayo Clinic from Merck, Boston Biomedical, Treos Bio, Taiho, Senhwa Pharmaceuticals, Bayer, Incyte, TriOncology, Seattle Genetics and Hutchison MediPharma. The funders had no role in the collection, analyses or interpretation of data or the writing of the manuscript.

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