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Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma

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Abstract

Background

Gastroesophageal cancer is a major cause of cancer-related mortality worldwide. Treatment of both early stage and advanced disease remains highly reliant on cytotoxic chemotherapy. About 4–24% of gastroesophageal cancers are microsatellite instability high (MSI-H). The MSI-H subtype is associated with favorable prognosis, resistance to cytotoxic chemotherapy, and sensitivity to immune checkpoint inhibitors (ICI). Recent studies have demonstrated promising activity of ICIs in the MSI-H subtype, resulting in fundamental changes in the management of MSI-H gastroesophageal adenocarcinoma.

Purpose

In this review, we discuss the prevalence, characteristics, prognosis, and management of MSI-H gastroesophageal adenocarcinoma, with a focus on recent and ongoing studies that have changed the landscape of treatment for the MSI-H subtype. We also discuss current challenges in the management of resectable and advanced MSI-H gastroesophageal cancer, including the need for more accurate biomarkers of response to ICI therapy.

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No datasets were generated or analysed during the current study.

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Funding

Author KZ is supported by the Duke Hematology & Transfusion Medicine Training Program (T32 HL007057). Author BA is supported by the following funding sources: NIH/NCI R37 Merit (5R37-CA249085), NIH/NCI R01 (5R01-CA251136), DoD Idea Award (W81XWH2110847), Duke Health Scholars Award, Duke Strong Start Award, ASCO/CCF, and Cancer Research Institute.

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  1. Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA

    Katherine I. Zhou, Brent A. Hanks & John H. Strickler

  2. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA

    Brent A. Hanks

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JS received the invitation to write this review and planned the structure of the manuscript. KZ wrote the first draft of the manuscript. JS and BH critically revised the manuscript.

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Author KZ reports no financial or non-financial competing interests. Author BH reports contracted research with Merck, Tempest, Lyell, Iovance, and Exicure, and advisory roles at Compugen and Astellas. Author JS reports compensation for a consultant or advisory role at Abbvie, AstraZeneca, Bayer, Beigene, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Jazz Pharmaceuticals, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Seagen, Taiho, Takeda, and Xilio Therapeutics. JS also reports research funding or contracted research with Abbvie, Amgen, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Roche/Genentech, and Seagen.

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Zhou, K.I., Hanks, B.A. & Strickler, J.H. Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma. J Gastrointest Canc (2023). https://doi.org/10.1007/s12029-023-01003-5

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