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

Nisha Pillay1, Rosie M Brady2, Malini Dey2

  • 1Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Cancer Research Centre, Wilmslow Rd, Manchester, M20 4GJ, UK; Divisions of Structural Biology & Cancer Biology, The Institute of Cancer Research (ICR), London, SW7 3RP, UK.

Progress in Biophysics and Molecular Biology
|February 1, 2021
PubMed

Insights

Poly (ADP-ribosyl)ation is crucial for genome stability. New poly (ADP-ribose)glycohydrolase (PARG) inhibitors show promise against cancer, offering a new strategy alongside PARP inhibitors for ovarian cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Poly (ADP-ribosyl)ation is vital for genome stability, DNA repair, and replication.
  • Cancer cells often have disrupted genome maintenance pathways.
  • Poly (ADP-ribose) polymerase (PARP) inhibitors are effective in BRCA-mutant ovarian cancers but face resistance.

Purpose of the Study:

  • To explore the role of poly (ADP-ribosyl)ation in genome stability.
  • To evaluate poly (ADP-ribose)glycohydrolase (PARG) inhibitors as a novel cancer therapy.
  • To position PARG inhibitors as a complementary strategy to PARP inhibitors for ovarian cancer.

Main Methods:

  • Review of the role of poly (ADP-ribosyl)ation in genome maintenance.
  • Discussion of the distinct anti-cancer activity of PARG inhibitors in vitro.
  • Analysis of therapeutic strategies targeting PARP inhibitor resistance.

Main Results:

  • Poly (ADP-ribosyl)ation pathways are frequently altered in cancer.
  • PARG inhibitors demonstrate anti-cancer effects distinct from PARP inhibitors.
  • PARG inhibition presents a potential therapeutic avenue for resistant tumors.

Conclusions:

  • Targeting poly (ADP-ribosyl)ation offers a viable strategy for cancer treatment.
  • PARG inhibitors represent a promising alternative and complementary approach to PARP inhibitors.
  • Further research into PARG inhibitors is warranted for overcoming PARP resistance in ovarian cancer.
Keywords:
Ovarian cancerPoly (ADP-ribose)glycohydolasePoly (ADP-ribosyl)ationReplication stress

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