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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
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
                           adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
               long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
               indicate if changes were made.

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