Immunotherapy and metastatic colorectal cancers with microsatellite instability or mismatch repair deficiency

Bull Cancer. 2019 Feb;106(2):137-142. doi: 10.1016/j.bulcan.2018.09.004. Epub 2018 Oct 14.

Abstract

Microsatellite instability (MSI) is a molecular indicator of defective DNA mismatch repair (dMMR) and is observed in approximately 5% of metastatic colorectal cancers (mCRC). MSI is a major predictive biomarker for the efficacy of immune checkpoint inhibitors (ICKi) amongst mCRC patients. After summarizing the literature about the efficacy of conventional cytotoxic regimens, we will highlight studies that have demonstrated the clinical activity of ICKi for patients with chemoresistant MSI/dMMR mCRC. Then we will focus on ongoing clinical trials and emerging challenges for the treatment of patients with MSI/dMMR mCRC.

Keywords: BRAF; Colorectal cancer; Immune checkpoint; Lynch syndrome; Microsatellite instability; Mismatch repair.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / therapy*
  • DNA Mismatch Repair*
  • Humans
  • Immunotherapy* / adverse effects
  • Ipilimumab / adverse effects
  • Ipilimumab / therapeutic use
  • Microsatellite Instability*
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Ipilimumab
  • Nivolumab
  • pembrolizumab