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Cancer Drug Resist 2022;5:[Accepted].10.20517/cdr.2022.73© The Author(s) 2022
Accepted Manuscript
Open AccessCommentary

New perspectives on epigenetic modifications and PARP inhibitor resistance in HR-deficient cancers

Correspondence Address: Dr. Martin Higgs, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, B15 2TT, UK. E-mail:


© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (, 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.


The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP) ribose polymerase (PARP) inhibitors. However, the efficacy of these compounds is hampered by resistance, which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage. Here, we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance. We discuss the implications, with a particular focus on epigenetic modifications and H3K4 methylation. We also deliberate on the mechanisms responsible, the implications for the refinement of PARP inhibitor use in the clinic, and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.

Cite This Article

Bayley R, Sweatman E, Higgs MR. New perspectives on epigenetic modifications and PARP inhibitor resistance in HR-deficient cancers. Cancer Drug Resist 2022;5:[Accept].

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