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


CONCLUSIONS
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.


CONCLUSIONS
Available evidence suggests that MSI-H CRC have different behaviour patterns and response to chemotherapy compared with MSS CRC.
Warusavitarne
Janindra
J
Department of Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St. Leonards, NSW, 2065, Australia. janindra@bigpond.com
Schnitzler
Margaret
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D053842:Microsatellite Instability / Q000187:drug effects*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein