Interplay between altered metabolism and DNA damage and repair in ovarian cancer

Sep 21, 2026

Ovarian cancer is the most lethal gynecological malignancy and is often linked to DNA repair deficiency and extensive metabolic reprogramming. Emerging evidence suggests that crosstalk between these pathways shapes ovarian cancer phenotypes, including resistance to DNA-damaging standard-of-care agents. This review summarizes current knowledge on metabolic rewiring in ovarian cancer and how DNA repair proteins can drive metabolic changes, including insights from other cancers. It also highlights therapeutic implications of altered DNA repair mechanism selection and targeted combination strategies.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages27

Reading Time1 h 8 min

AccessFree to download

Abstract

Introduction

Ovarian Cancer and Treatment

Treatment approaches

Homologous recombination status

Author Manuscript Author Manuscript Author Manuscript Author Manuscript | | HHS Public Access
Author manuscript
Bioessays. Author manuscript; available in PMC 2025 March 31. | | --- | --- | Published in final edited form as: Bioessays. 2024 August ; 46(8): e2300166 . doi:10.1002/bies.202300166 . Interplay between altered metabolism and DNA damage and repair in ovarian cancer Apoorva Uboveja, Katherine M. Aird Department of Pharmacology & Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Abstract Ovarian cancer is the most lethal gynecological malignancy and is often associated with both DNA repair deficiency and extensive metabolic reprogramming. While still emerging, the interplay between these pathways can affect ovarian cancer phenotypes, including therapeutic resistance to the DNA damaging agents that are standard-of-care for this tumor type. In this review, we will discuss what is currently known about cellular metabolic rewiring in ovarian cancer that may impact DNA damage and repair in addition to highlighting how specific DNA repair proteins also promote metabolic changes. We will also discuss relevant data from other cancers that could be used to inform ovarian cancer therapeutic strategies. Changes in the choice of DNA repair mechanism adopted by ovarian cancer are a major factor in promoting therapeutic resistance. Therefore, the impact of metabolic reprogramming on DNA repair mechanisms in ovarian cancer has major clinical implications for targeted combination therapies for the treatment of this devastating disease. Keywords chemoresistance; cisplatin; homologous recombination; metabolites; PARP inhibitors INTRODUCTION Over the past decade, the scientific community has made remarkable progress in understanding altered metabolism exhibited by tumor cells. Tumor cells reprogram their metabolism to support their high metabolic demands and adapt to changes in their microenvironment. [1] Through this work, many labs have demonstrated that rewired tumor metabolism significantly impacts DNA repair processes, which has broadened our knowledge on how metabolic perturbations might affect DNA repair. Interestingly, this This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Correspondence: Katherine M. Aird, Department of Pharmacology & Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, 5051 Centre Ave. Office: 2041; Lab: 2050, Pittsburgh, PA 15213, USA., [katherine.aird@pitt.edu](katherine.aird@pitt.edu). AUTHOR CONTRIBUTIONS Apoorva Uboveja and Katherine M. Aird conceptualized and drafted the manuscript. CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Uboveja and Aird Page 2 crosstalk is not one-sided – various DNA repair processes are known to modulate metabolic pathways. It is well-established that DNA repair pathways play a pivotal role in cancer progression because dysregulation of DNA repair can lead to increased mutation rate and enhanced genomic instability. Accumulating evidence highlights multiple mechanisms through which metabolic perturbations are thought to impact DNA damage and repair, including redox homeostasis that limits DNA damage, increasing nucleotides needed for repair, and chromatin remodeling and relaxation to allow for enhanced repair. Moreover, alterations in DNA repair genes are common in many cancers, and many of these proteins including BRCA1, ataxia telangiectasia mutated (ATM), and ATR have been linked to changes in metabolism. Uncovering new links between cancer metabolism and DNA repair pathways may provide new targeted therapies to use in comb

FAQs

Why is the interaction between metabolism and DNA repair important in ovarian cancer?

Ovarian cancer often shows both DNA repair deficiency and metabolic reprogramming. Their interplay can influence tumor phenotypes, including resistance to DNA-damaging therapies.

What does the review focus on regarding metabolic rewiring?

It discusses cellular metabolic rewiring in ovarian cancer and explains how metabolic changes can impact DNA damage and repair processes.

How does homologous recombination status relate to treatment considerations?

HGSOC is associated with homologous recombination deficiency in many cases, while HR-proficient tumors often carry genetic alterations driving cell cycle dysregulation. Assessing HR status becomes essential in the clinical setting.

Sep 21, 2026

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