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DNA repair and the contribution to chemotherapy resistance

Ksenija Nesic1,2, Phoebe Parker3, Elizabeth M Swisher4

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.

Genome Medicine
|May 26, 2025
PubMed

Insights

Cancer cells

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • The DNA damage response (DDR) is crucial for cell survival against DNA damaging agents.
  • Cancer cells often have altered DNA repair pathways, leading to genomic instability.
  • Chemotherapeutics exploit DNA breaks, creating a therapeutic window.

Purpose of the Study:

  • To review the DNA damaging mechanisms of various chemotherapeutics.
  • To discuss how DNA repair and avoidance of double-strand breaks contribute to therapy resistance.
  • To explore strategies for overcoming chemotherapy resistance.

Main Methods:

  • Literature review of DNA damaging agents and resistance mechanisms.
  • Analysis of the interplay between DNA repair pathways and therapeutic outcomes.
  • Synthesis of current research on counteracting therapy resistance.

Main Results:

  • Chemotherapy effectiveness relies on inducing DNA double-strand breaks.
  • Therapy resistance arises from mechanisms that prevent DNA breaks or enhance repair.
  • Altered DNA repair pathways in cancer contribute to both instability and resistance.

Conclusions:

  • Understanding DDR is key to cancer therapy.
  • Targeting DNA repair mechanisms may overcome resistance.
  • Developing novel strategies to counteract resistance is essential for effective cancer treatment.
Keywords:
Chemotherapy resistanceDNA damage responseDNA repair

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