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van Waardenburg et al. Cancer Drug Resist 2021;4:837-41 Cancer
DOI: 10.20517/cdr.2021.80
Drug Resistance

Editorial Open Access

Targeting DNA repair pathways to overcome cancer
drug resistance

1,3
Robert C.A.M. van Waardenburg , Eddy S. Yang 1,2,3
1
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
2
Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
3
O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Correspondence to: Dr. Robert C.A.M. van Waardenburg, PhD, Department of Pharmacology and Toxicology, University of
Alabama at Birmingham, 155 Volker Hall, 1670 University Boulevard, Birmingham, AL 35294-0019, USA.
E-mail: rvanwaar@uab.edu; Dr. Eddy S. Yang, MD, PhD, Department of Radiation Oncology, University of Alabama at
Birmingham, 1700 6th Ave South, HSROC Suite 2232, Birmingham, AL 35249-6832, USA. E-mail: shyang@uabmc.edu
How to cite this article: van Waardenburg RCAM, Yang ES. Targeting DNA repair pathways to overcome cancer drug resistance.
Cancer Drug Resist 2021;4:837-41. https://dx.doi.org/10.20517/cdr.2021.80

Received: 10 Aug 2021 Accepted: 13 Aug 2021 Available online: 19 Aug 2021
Academic Editor: Godefridus J. Peters Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

DNA damage response and DNA repair pathways are evolutionarily conserved from prokaryotes to
eukaryotes to protect the host from genomic instability. Dysregulation of proteins involved in these
pathways in mammalian cells increases genomic alterations leading to genomic instability, a well-
established hallmark of cancer . However, our understanding of the signaling pathways to repair DNA
[1,2]
damage in cancers has grown exponentially over the last decades. Because one of the mainstays of successful
cancer treatments acts through generating DNA damage, the growth of understanding these pathways have
led to emerging and promising strategies of targeting the DNA damage response and DNA repair pathways
to enhance cancer cell sensitivity to current chemotherapeutic agents. Additionally, understanding this
biology can also improve the therapeutic index, which emphasizes the effective killing of cancer cells while
sparing healthy cells in the patient. Moreover, by targeting signaling and repair of DNA lesions, we aim to
prevent compensatory activation of DNA repair pathways as a resistance mechanism. As such, the concept
of targeting DNA repair has been successfully developed in the last decade to a bona fide therapeutic
strategy with poly (ADP-ribose) polymerase inhibitors (PARPi) to treat DNA repair deficient breast,
ovarian, pancreatic, and prostate cancers . These successes have stimulated the clinical development of
[3-9]
small molecules that target other key components of the DNA damage response and repair pathways. These

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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