Platinum Resistance in Ovarian Cancer: Role of DNA Repair

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. It is initially responsive to cisplatin and carboplatin, two DNA damaging agents used in first line therapy. However, almost invariably, patients relapse with a tumor resistant to subsequent treatment with platinum containing d...

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Bibliographic Details
Published in:Cancers 2019-01, Vol.11 (1), p.119
Main Authors: Damia, Giovanna, Broggini, Massimo
Format: Article
Language:English
Subjects:
Adducts
Cancer therapies
Carboplatin
Cell cycle
Chemotherapy
Cisplatin
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Drug delivery
Drug development
Drug resistance
Epigenetics
Gene deletion
Kinases
Metastasis
Mutation
Ovarian cancer
Platinum
Point mutation
Proteins
Review
Tumors
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Summary:Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. It is initially responsive to cisplatin and carboplatin, two DNA damaging agents used in first line therapy. However, almost invariably, patients relapse with a tumor resistant to subsequent treatment with platinum containing drugs. Several mechanisms associated with the development of acquired drug resistance have been reported. Here we focused our attention on DNA repair mechanisms, which are fundamental for recognition and removal of platinum adducts and hence for the ability of these drugs to exert their activity. We analyzed the major DNA repair pathways potentially involved in drug resistance, detailing gene mutation, duplication or deletion as well as polymorphisms as potential biomarkers for drug resistance development. We dissected potential ways to overcome DNA repair-associated drug resistance thanks to the development of new combinations and/or drugs directly targeting DNA repair proteins or taking advantage of the vulnerability arising from DNA repair defects in EOCs.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11010119