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Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas

1
Department of Oncology, University of Torino, Candiolo, 10060 Torino, Italy
2
Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142 Km 3.95, Candiolo, 10060 Torino, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1315; https://doi.org/10.3390/cancers12051315
Received: 8 April 2020 / Revised: 15 May 2020 / Accepted: 19 May 2020 / Published: 21 May 2020
(This article belongs to the Section Cancer Therapy)
Despite significant improvements in surgical and medical management, high grade serous ovarian cancer (HGSOC) still represents the deadliest gynecologic malignancy and the fifth most frequent cause of cancer-related mortality in women in the USA. Since DNA repair alterations are regarded as the “the Achille’s heel” of HGSOC, both DNA homologous recombination and DNA mismatch repair deficiencies have been explored and targeted in epithelial ovarian cancers in the latest years. In this review, we aim at focusing on the therapeutic issues deriving from a faulty DNA repair machinery in epithelial ovarian cancers, starting from existing and well-established treatments and investigating new therapeutic approaches which could possibly improve ovarian cancer patients’ survival outcomes in the near future. In particular, we concentrate on the role of both Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPis) and immune checkpoint inhibitors in HGSOC, highlighting their activity in relation to BRCA1/2 mutational status and homologous recombination deficiency (HRD). We investigate the biological rationale supporting their use in the clinical setting, pointing at tracking their route from the laboratory bench to the patient’s bedside. Finally, we deal with the onset of mechanisms of primary and acquired resistance to PARPis, reporting the pioneering strategies aimed at converting homologous-recombination (HR) proficient tumors into homologous recombination (HR)-deficient HGSOC. View Full-Text
Keywords: epithelial ovarian cancer; DNA repair deficiency; DNA homologous recombination; DNA mismatch repair; PARP inhibitors; BRCA reversion mutations epithelial ovarian cancer; DNA repair deficiency; DNA homologous recombination; DNA mismatch repair; PARP inhibitors; BRCA reversion mutations
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MDPI and ACS Style

Milanesio, M.C.; Giordano, S.; Valabrega, G. Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas. Cancers 2020, 12, 1315. https://doi.org/10.3390/cancers12051315

AMA Style

Milanesio MC, Giordano S, Valabrega G. Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas. Cancers. 2020; 12(5):1315. https://doi.org/10.3390/cancers12051315

Chicago/Turabian Style

Milanesio, Michela C., Silvia Giordano, and Giorgio Valabrega. 2020. "Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas" Cancers 12, no. 5: 1315. https://doi.org/10.3390/cancers12051315

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