title: Targeting Mismatch Repair defects: A novel strategy for personalized cancer treatment.
abstract: The DNA Mismatch Repair (MMR) pathway is a fundamental cellular process required to repair mispaired bases introduced routinely during DNA replication. Given this critical role in the maintenance of genome stability, it is not surprising that underlying defects in the MMR pathway occur in both hereditary and sporadic cancers. Furthermore, the MMR status greatly influences the sensitivity of cells to many common chemotherapeutic agents. Therefore, novel strategies are being investigated to exploit the loss of MMR in these cancers and to identify personalized therapeutic strategies to target MMR deficient tumours. In this review, we describe recent advances in strategies to target MMR deficient tumours using a synthetic lethal approach. We discuss new ways to target mutations secondary to MMR deficiency and suggest potential new therapies to optimise treatment outcome. We highlight ongoing clinical studies focussing on novel ways of preventing and treating MMR deficient cancers.
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1 M 6BQ, UK.
authors.forename: Rumena
authors.initials: R
authors.lastname: Begum
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1 M 6BQ, UK. Electronic address: sarah.martin@qmul.ac.uk.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Martin
mesh_terms: D063646:Carcinogenesis / Q000473:pathology; D002986:Clinical Trials as Topic; D053843:DNA Mismatch Repair; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000628:therapy*; D057285:Precision Medicine
keywords: Mismatch Repair; Synthetic lethality; Therapies