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Open Access Translating Mismatch Repair Mechanism into Cancer Care

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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.
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Keywords: Alkylating agents; Lynch syndrome; chemoresistance; cisplatin; colorectal cancer; microsatellite instability; mismatch repair

Document Type: Research Article

Publication date: January 1, 2014

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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