Therapeutic targeting of the DNA mismatch repair pathway

Clin Cancer Res. 2010 Nov 1;16(21):5107-13. doi: 10.1158/1078-0432.CCR-10-0821. Epub 2010 Sep 7.


The mismatch repair (MMR) pathway is involved in the removal of DNA base mismatches that arise either during DNA replication or are caused by DNA damage. Mutations in four genes involved in MMR, MSH2, MLH1, PMS2 and MSH6, predispose to a range of tumorigenic conditions, including hereditary nonpolyposis colon cancer, also known as Lynch syndrome. Here we discuss the canonical MMR pathway and the burgeoning evidence for noncanonical roles for the MMR genes, and highlight the therapeutic implications of MMR. In particular, we discuss how the DNA repair defect in MMR-deficient cancers could be exploited by the development of novel therapeutic strategies based on synthetic lethal approaches.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • DNA Mismatch Repair / drug effects
  • DNA Mismatch Repair / genetics*
  • Humans
  • Medical Oncology / trends
  • Models, Biological
  • Molecular Targeted Therapy / methods*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Translational Research, Biomedical / trends


  • Antineoplastic Agents
  • Nuclear Proteins