Targeting the DNA Damage Response for Cancer Therapy

Int J Mol Sci. 2023 Nov 2;24(21):15907. doi: 10.3390/ijms242115907.

Abstract

Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucidates the DNA damage repair pathways and the progress made in targeting key proteins within these pathways for cancer treatment. Among them, poly (ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DDR, and inhibitors targeting PARP1 have garnered extensive attention in anticancer research. By delving into the realms of DNA damage and repair, we aspire to explore more precise and effective strategies for cancer therapy and to seek novel avenues for intervention.

Keywords: DNA damage response; DNA repair; PARP1; cancer therapy; double-strand DNA break repair.

Publication types

  • Review

MeSH terms

  • DNA Damage
  • DNA Repair*
  • Genomic Instability
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly (ADP-Ribose) Polymerase-1