Title:Translating Mismatch Repair Mechanism into Cancer Care
Volume: 15
Issue: 1
Author(s): Christopher D. Heinen
Affiliation:
Keywords:
Alkylating agents, chemoresistance, cisplatin, colorectal cancer, Lynch syndrome, microsatellite instability, mismatch
repair.
Abstract: The first DNA mismatch repair gene was identified in Escherichia coli nearly fifty years ago. Since then, five
decades of basic biomedical research on this important repair pathway have led to an extensive understanding of its molecular
mechanism. The significance of this work was clearly highlighted in the early 1990’s when mutations in the human
homologs of the mismatch repair genes were identified as responsible for Lynch syndrome (also known as hereditary
non-polyposis colon cancer), the most common form of hereditary colorectal cancer. Basic science research on mismatch
repair in lower organisms directly led researchers to the discovery of this link between defective mismatch repair and cancer
and continues to guide clinical decisions today. The knowledge that disrupted mismatch repair function gives rise to
the nucleotide-level form of genomic instability called microsatellite instability continues to be an important diagnostic
tool for identifying Lynch syndrome patients as well as sporadic cancer patients who suffer from mismatch repairdefective
cancers. Today, clinicians are using the information about mismatch repair molecular mechanism to guide decisions
about cancer therapy as well to devise new therapies. In this review, we will examine what is known about the molecular
function of the human mismatch repair pathway. We will highlight how this information is being used in cancer
diagnosis and treatment. We will also discuss strategies being designed to target the 10-15% of colorectal, endometrial,
ovarian and other cancers with defective mismatch repair.
