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International Journal of Molecular Sciences

International Journal of Molecular Sciences

IF: 5.6
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Different Patterns of Platinum Resistance in Ovarian Cancer Cells with Homologous Recombination Proficient and Deficient Background

Published:6 March 2024 DOI: 10.3390/ijms25053049
Michela Chiappa, Federica Guffanti, Chiara Grasselli, Nicolò Panini, Alessandro Corbelli, Fabio Fiordaliso, Giovanna Damia

Abstract

Platinum compounds are very active in first-line treatments of ovarian carcinoma. In fact, high rates of complete remission are achieved, but most patients eventually relapse with resistant disease. Many mechanisms underlying the platinum-resistant phenotype have been reported. However, there are no data in the same isogenic cell system proficient and deficient in homologous recombination (HR) on platinum-acquired resistance that might unequivocally clarify the most important mechanism associated with resistance. We generated and characterized cisplatin (DDP)-resistant murine ovarian ID8 cell lines in a HR-deficient and -proficient background. Specific upregulation of the NER pathway in the HR-proficient and -resistant cells and partial restoration of HR in Brca1?/?-resistant cells were found. Combinations of different inhibitors of the DNA damage response pathways with cisplatin were strongly active in both resistant and parental cells. The data from the ID8 isogenic system are in line with current experimental and clinical evidence and strongly suggest that platinum resistance develops in different ways depending on the cell DNA repair status (i.e., HR-proficient or HR-deficient), and the upregulation and/or restoration of repair pathways are major determinants of DDP resistance.

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Procduct Name CAS Molecular Formula Supplier Price
Olaparib 763113-22-0 C24H23FN4O3 699 suppliers $11.00-$2994.75
Olaparib 763113-22-0 C24H23FN4O3 699 suppliers $11.00-$2994.75
Olaparib 763113-22-0 C24H23FN4O3 699 suppliers $11.00-$2994.75
Olaparib 763113-22-0 C24H23FN4O3 699 suppliers $11.00-$2994.75
AZD2281 763113-22-0 C24H23FN4O3 - Inquiry
AZD2281 763113-22-0 C24H23FN4O3 - Inquiry
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