The role of chemotherapy in microsatellite unstable (MSI-H) colorectal cancer

Int J Colorectal Dis. 2007 Jul;22(7):739-48. doi: 10.1007/s00384-006-0228-0. Epub 2006 Nov 16.

Abstract

Introduction: High-frequency microsatellite instability (MSI-H) is an alternate pathway of colorectal carcinogenesis, which accounts for 15% of all sporadic colorectal cancers. These tumours arise from mutations in the DNA mismatch repair system and thus have different responses to chemotherapeutic agents compared to microsatellite stable (MSS) cancers.

Objective: This review aims to summarise the available literature on the responses to chemotherapy in MSI-H colorectal cancer (CRC).

Results and discussion: 5 Fluorouracil (5FU) is commonly used as a chemotherapeutic agent in colon cancer and in vitro evidence shows reduced response to 5FU in MSI-H CRC. The clinical evidence is conflicting but favours a reduced response to 5FU in MSI-H CRC. Several newer agents such as COX-2 inhibitors and irinotecan are also reviewed.

Conclusion: Available evidence suggests that MSI-H CRC have different behaviour patterns and response to chemotherapy compared with MSS CRC.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / epidemiology
  • Colorectal Neoplasms* / genetics
  • DNA Repair
  • DNA, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Microsatellite Instability / drug effects*
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein / genetics
  • Mutation / drug effects
  • Nuclear Proteins / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • DNA, Neoplasm
  • MLH1 protein, human
  • Nuclear Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein