Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combination therapeutics

Bhattacharjee, S., Nandi, S. (December 2017) Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combination therapeutics. IUBMB Life, 69 (12). pp. 929-937. ISSN 1521-6543

DOI: 10.1002/iub.1696


Synthetic lethality refers to a lethal phenotype that results from the simultaneous disruptions of two genes, while the disruption of either gene alone is viable. Many DNA double strand break repair (DSBR) genes have synthetic lethal relationships with oncogenes and tumor suppressor genes, which can be exploited for targeted cancer therapy, an approach referred to as combination therapy. DNA double-strand breaks (DSBs) are one of the most toxic lesions to a cell and can be repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). HR and NHEJ genes are particularly attractive targets for cancer therapy because these genes have altered expression patterns in cancer cells when compared with normal cells and these genetic abnormalities can be targeted for selectively killing cancer cells. Here, we review recent advances in the development of small molecule inhibitors against HR and NHEJ genes to induce synthetic lethality and address the future directions and clinical relevance of this approach. (c) 2017 IUBMB Life, 69(12):929-937, 2017.

Item Type: Paper
Uncontrolled Keywords: DNA double strand break repair clinical trials combination therapy drug discovery genomic instability homologous recombination non-homologous end joining precision medicine synthetic lethality targeted cancer therapy
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL labs > Martienssen lab
CSHL labs > Stillman lab
Depositing User: Matt Covey
Date: December 2017
Date Deposited: 01 Dec 2017 21:54
Last Modified: 01 Dec 2017 21:54
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