Platinum Resistance in Ovarian Cancer: Role of DNA Repair

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Jan 24

PMID 30669514

Citations 138

Authors

Giovanna Damia

Massimo Broggini

Affiliations

Soon will be listed here.

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.

Citing Articles

Advanced Therapeutic Approaches for Metastatic Ovarian Cancer.

Choe S, Jeon M, Yoon H Cancers (Basel). 2025; 17(5).

PMID: 40075635 PMC: 11898553. DOI: 10.3390/cancers17050788.

Coordinated protein modules define DNA damage responses to carboplatin at single cell resolution in human ovarian carcinoma models.

Bedia J, Huang Y, Gonzalez A, Gonzalez V, Funingana I, Rahil Z bioRxiv. 2024; .

PMID: 39605494 PMC: 11601625. DOI: 10.1101/2024.11.21.624591.

Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022.

Cabarca S, Ili C, Vanegas C, Gil L, Vertel-Morrinson M, Brebi P Front Oncol. 2024; 14:1450675.

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Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway.

Li Z, Wu Y, Guo Y, Min X, Lin Y Korean J Physiol Pharmacol. 2024; 29(2):191-204.

PMID: 39539173 PMC: 11842298. DOI: 10.4196/kjpp.24.132.

Unlocking the potential of immunotherapy in platinum-resistant ovarian cancer: rationale, challenges, and novel strategies.

Kefas J, Flynn M Cancer Drug Resist. 2024; 7:39.

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