The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
PARP inhibitors: Synthetic lethality in the clinic
Open accessAbstract
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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Cites
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
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Self-citationSpecific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
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Self-citationWhole genomes redefine the mutational landscape of pancreatic cancer
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“Large-scale cancer genome sequencing projects also revealed that somatic mutations in genes involved in HRR occur in a wide spectrum of tumors (34), in particular in significant fractions of high-grade serous ovarian cancer (HGS-OVCa) (38), advanced prostate cancer (39) and pancreatic cancer (40, 41).”
BackgroundDNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
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Cited by
Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation
Litton, J. K., Rugo, H. S., Ettl, J., Hurvitz, S. A., Gonçalves, A., Lee, K.-H., Fehrenbacher, L., Yerushalmi, R., Mina, L. A., Martin, M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1802905 · Cited by 2,175
DNA double-strand break repair-pathway choice in somatic mammalian cells
Scully, R., Panday, A., Elango, R., & Willis, N. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0152-0 · Cited by 1,457
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs
Bianchini, G., De Angelis, C., Licata, L., & Gianni, L. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00565-2 · Cited by 1,382
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
State-of-the-art strategies for targeting the DNA damage response in cancer
Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0114-z · Cited by 1,189
Metadata
- Authors
- Lord, C. J., & Ashworth, A.
- Venue
- Science
- Published
- 2017-03-17
- Volume
- 355
- Issue
- 6330
- Pages
- 1152-1158
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2597062310
- Cited by
- 2,880
- References
- 9
- FWCI
- 81.21
- Type
- journal article
- Language
- en
- Open access
- green
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