Epigenetic deregulation of DNA repair and its potential for therapy

Monika E. Hegi, Davide Sciuscio, Anastasia Murat, Marc Levivier, Roger Stupp

Research output: Contribution to journalReview article

43 Scopus citations

Abstract

Epigenetic silencing of essential components of DNA repair pathways is a common event in many tumor types, and comprise O6-methylguanine-DNA methyltransferase (MGMT), human mut L homolog 1 (hMLH1), Werner syndrome gene (WRN), breast cancer susceptibility gene 1 (BRCA1), and genes of the Fanconi anemia pathway. Most interestingly, some of these alterations become the Achilles heel of the affected tumors upon treatment with certain classes of anticancer agents. That is, patients whose tumors carry such defects can be stratified for respective therapy rendering some classic DNA damaging agents, such as alkylators or DNA crosslinking agents, into "targeted therapies." Here we review some of the affected repair pathways that, when inactivated, sensitize the tumors to specific drugs and are thus exploitable for individualized therapy.

Original languageEnglish (US)
Pages (from-to)5026-5031
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number16
DOIs
Publication statusPublished - Aug 15 2009

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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