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Cancers 2019, 11(1), 119; https://doi.org/10.3390/cancers11010119

Platinum Resistance in Ovarian Cancer: Role of DNA Repair

Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via G. La Masa 19, 20156 Milan, Italy
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Received: 5 November 2018 / Revised: 15 January 2019 / Accepted: 17 January 2019 / Published: 20 January 2019
(This article belongs to the Special Issue Cancer Chemoresistance)
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Abstract

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. View Full-Text
Keywords: ovarian cancer; nucleotide excision repair; DNA damage response; DNA repair; homologous recombination; DNA damaging agents; cisplatin; DNA polymorphisms; gene mutations; drug resistance ovarian cancer; nucleotide excision repair; DNA damage response; DNA repair; homologous recombination; DNA damaging agents; cisplatin; DNA polymorphisms; gene mutations; drug resistance
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Damia, G.; Broggini, M. Platinum Resistance in Ovarian Cancer: Role of DNA Repair. Cancers 2019, 11, 119.

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