Evolving Strategies in the Management of Microsatellite Instability-High/Mismatch Repair Deficient Esophagogastric Adenocarcinoma

Curr Oncol Rep. 2025 Feb;27(2):81-94. doi: 10.1007/s11912-024-01624-4. Epub 2025 Jan 3.

Abstract

Purpose of review: This review addresses the current treatment paradigm and new advancements in the management of microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) esophagogastric cancer (EGC).

Recent findings: While chemotherapy and surgery remain the cornerstone of EGC treatment, MSI-H/dMMR tumors harbor high tumor mutational burden and represent a subset of patients who benefit from immune checkpoint inhibitors (ICI). ICI has been incorporated in the front line setting with and without chemotherapy for advanced disease. Recently, ICI has been studied in the perioperative setting for resectable disease. Though perioperative ICI results in improved response rates, it is not yet clear whether this translates to a survival benefit. Despite high response rates with ICI in this patient population, many do not respond to therapy, representing a major challenge in treatment. Preclinical studies have highlighted potential mechanisms of resistance which will guide drug development and clinical trials.

Keywords: Deficient mismatch repair; Esophageal cancer; Esophagogastric cancer; Gastric cancer; Immunotherapy; Microsatellite instability high.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / therapy
  • DNA Mismatch Repair*
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Microsatellite Instability*
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy

Substances

  • Immune Checkpoint Inhibitors