期刊
SCIENCE
卷 355, 期 6330, 页码 1152-1158出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aam7344
关键词
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资金
- Breast Cancer Now
- Cancer Research UK
- National Health Service
- Susan G. Komen for the Cure
- Breast Cancer Research Foundation
- BRCA Foundation
- UCSF
- AtlasMDX
- Third Rock Ventures
- Pfizer
- Merck Serono
- AstraZeneca
- Tango Therapeutics
- Sun Pharma
- Cancer Research UK [14276, 24439, 25237] Funding Source: researchfish
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors arising in patients who carry germline mutations in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair defect. PARPi also show promising activity in more common cancers that share this repair defect. However, as with other targeted therapies, resistance to PARPi arises in advanced disease. In addition, determining the optimal use of PARPi within drug combination approaches has been challenging. Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical approval provide interesting lessons for the development of other therapies. Here, we discuss current knowledge of PARP inhibitors and potential ways to maximize their clinical effectiveness.
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