DNA replication stress and emerging prospects for PARG inhibitors in ovarian cancer therapy.

Poly (ADP-ribosyl)ation has central functions in maintaining genome stability, including facilitating DNA replication and repair. In cancer cells these processes are frequently disrupted, and thus interfering with poly (ADP-ribosyl)ation can exacerbate inherent genome instability and induce selective cytotoxicity. Indeed, inhibitors of poly (ADP-ribose) polymerase (PARP) are having a major clinical impact in treating women with BRCA-mutant ovarian cancer, based on a defect in homologous recombination. However, only around half of ovarian cancers harbour defects in homologous recombination, and most sensitive tumours eventually acquire PARP inhibitor resistance with treatment. Thus, there is a pressing need to develop alternative treatment strategies to target tumours with both inherent and acquired resistance to PARP inhibition. Several novel inhibitors of poly (ADP-ribose)glycohydrolase (PARG) have been described, with promising anti-cancer activity in vitro that is distinct from PARP inhibitors. Here we discuss, the role of poly (ADP-ribosyl)ation in genome stability, and the potential for PARG inhibitors as a complementary strategy to PARP inhibitors in the treatment of ovarian cancer.

• Publication year

  2021

• Venue

  Progress in Biophysics and Molecular Biology

• Publication date

  2021-01-29

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.pbiomolbio.2021.01.004PMID 33524442
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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