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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 11
ISSUE: 10
DOI: 10.2174/1389450111007011336      Price:  $58









Targeting Synthetic Lethality in DNA Damage Repair Pathways as an Anti-Cancer Strategy

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Author(s): Benjamin J. Moeller, Wadih Arap and Renata Pasqualini
Pages 1336-1340 (5)
Abstract:
During the process of tumorigenesis, certain cancers are known to develop deficiencies in one or more major pathways of DNA damage repair, rendering them critically dependent on alternative repair processes for maintaining genomic integrity and viability. Targeting these alternative DNA repair mechanisms is a potentially highly-specific anticancer strategy, as their inhibition is theoretically toxic only to tumor cells and not to normal tissues. We will review here the rationale behind this strategy and provide examples of its application. We will also discuss several as yet unanswered questions surrounding this strategy, including whether human cancers frequently harbor synthetically lethal interactions in DNA repair and, if so, how patients might be identified who would benefit from targeting such interactions.
Keywords:
Radiation, chemotherapy, DNA repair, double-strand break repair, non-homologous end joining, homologous recombination, Tumorigenesis, Homologous recobmination, Mutation, Tumor-specific phenotype, PARP inhibitor, BRCA-defective tumors, Translocation, Genetic mutation, Amplification, Oncogenic stress, Cytotoxic drugs, Radiomimetics, NHEJ, PARP proteins, PARP inhibitors, Biomarkers, Oncology
Affiliation:
David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.