Mismatch repair deficient colorectal cancer in the era of personalized treatment.
The molecular and genetic subtyping of cancer has allowed the emergence of individualized therapies. This approach could potentially deliver treatments that have both increased efficacy as well as reduced toxicity. A well-defined subtype of colorectal cancer (CRC) is characterized by a deficiency in the mismatch repair (MMR) pathway. MMR deficiency not only contributes to the pathogenesis of a large proportion of CRC, but also determines the response to many of the drugs that are frequently used to treat this disease. In this Review we describe the MMR deficient phenotype and discuss how a deficiency in this DNA repair process may impact on the management of CRC, including surgery, adjuvant chemotherapy and the choice of systemic agents for the palliation of advanced disease. We also discuss how the DNA repair defect in MMR deficient CRC could be exploited in the development of novel therapeutic strategies.
Hewish
Madeleine
M
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Lord
Christopher J
CJ
Martin
Sarah A
SA
Cunningham
David
D
Ashworth
Alan
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D016001:Confidence Intervals; D053843:DNA Mismatch Repair / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis
D000970:Antineoplastic Agents; D017671:Platinum Compounds