Journal article
Defective DNA repair in hereditary ovarian cancers: Implications for therapy
American journal of health-system pharmacy, Vol.75(21), pp.1697-1707
11/01/2018
DOI: 10.2146/ajhp180124
PMID: 30228165
Abstract
Purpose. The role of mutated DNA repair pathways in hereditary ovarian cancer (OC) and the clinical basis for the use of poly(ADP-ribose) polymerase (PARP) enzyme inhibitors and an immune checkpoint inhibitor as novel targeted therapies in the treatment of certain OC subtypes are reviewed.
Summary. OC is the most lethal of all gynecologic malignancies and encompasses a highly diverse collection of cancers. Hereditary OCs are a unique subtype of OC encompassing up to 24% of all OCs, including cancers driven by germline mutations of the BRCA1 or BRCA2 genes, mutations associated with Fanconi anemia (FA), BRCAness germline mutations, and Lynch syndrome. With an increasing wealth of genomic data available in cancer research, a common thread of defective DNA repair pathways as a primary driver of hereditary OCs has emerged. OCs driven by BRCA1/2, FA-associated, and BRCAness germline mutations have a demonstrated sensitivity to PARP inhibitors due to underlying deficiencies in DNA homologous recombination; however, clinical responses are often partial and highly dependent on platinum sensitivity. Additionally, the immune checkpoint inhibitor pembrolizumab is indicated for certain metastatic solid tumors characterized by microsatellite instability, a distinguishing feature highly associated with DNA mismatch repair deficiency in Lynch syndrome-associated cancers, including some OCs. Conclusion. In hereditary OC syndromes, mutations in DNA repair pathways form the clinical basis for the use of PARP inhibitors and an immune checkpoint inhibitor as novel targeted therapies.
Details
- Title: Subtitle
- Defective DNA repair in hereditary ovarian cancers: Implications for therapy
- Creators
- Brian T. Burgess - University of KentuckyJill M. Kolesar - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- American journal of health-system pharmacy, Vol.75(21), pp.1697-1707
- Publisher
- Oxford Univ Press
- DOI
- 10.2146/ajhp180124
- PMID
- 30228165
- ISSN
- 1079-2082
- eISSN
- 1535-2900
- Number of pages
- 11
- Language
- English
- Date published
- 11/01/2018
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695788002771
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