期刊
ANNUAL REVIEW OF MEDICINE, VOL 66
卷 66, 期 -, 页码 455-470出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-med-050913-022545
关键词
BRCA1; BRCA2; drug resistance; breast cancer; ovarian cancer
资金
- Cancer Research UK [14276] Funding Source: researchfish
- Cancer Research UK Funding Source: Medline
- Wellcome Trust Funding Source: Medline
The genetic concept of synthetic lethality, in which the combination or synthesis of mutations in multiple genes results in cell death, provides a framework to design novel therapeutic approaches to cancer. Already there are promising indications, from clinical trials exploiting this concept by using poly(ADP-ribose) polymerase (PARP) inhibitors in patients with germline BRCA1 or BRCA2 gene mutations, that this approach could be beneficial. We discuss the biological rationale for BRCA-PARP synthetic lethality, how the synthetic lethal approach is being assessed in the clinic, and how mechanisms of resistance are starting to be dissected. Applying the synthetic lethal concept to target non-BRCA-mutant cancers also has clear potential, and we discuss how some of the principles learned in developing PARP inhibitors might also drive the development of additional genetic approaches.
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