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The 'Pushmi-Pullyu' of DNA REPAIR: Clinical Synthetic Lethality

S Percy Ivy1, Johann de Bono2, Elise C Kohn1

  • 1Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, 9609 Medical Center Drive, Room 5W458, MSC 9739, Bethesda, MD 20852, USA.

Trends in Cancer
|July 26, 2017
PubMed

Insights

Genomic integrity is vital for survival. DNA repair inhibitors (DNARi) exploit cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genomic integrity is crucial for survival against environmental stress.
  • Cancer and its treatments disrupt DNA stability, creating therapeutic vulnerabilities.
  • Targeting DNA repair pathways offers a promising strategy for cancer therapy.

Purpose of the Study:

  • To review recent advancements in DNA repair inhibitors (DNARi).
  • To categorize DNARi based on their biofunctional roles in DNA damage response.
  • To explore future directions and clinical opportunities for DNARi in cancer treatment.

Main Methods:

  • Literature review of recent research on DNA repair and DNARi.
  • Classification of DNARi into five biofunctional categories: sensors, mediators, transducers, effectors, and collaborators.
  • Analysis of the 'pushmi-pullyu' effect of disrupted DNA repair in cancer therapy.

Main Results:

  • DNARi can be categorized by their roles in sensing DNA damage, signaling, checkpoint regulation, and microenvironment modulation.
  • Disrupting DNA repair can lead to synthetic lethality, selectively killing cancer cells.
  • New DNARi agents are emerging with potential for enhanced cancer treatment.

Conclusions:

  • DNARi represent a significant therapeutic strategy by exploiting cancer's reliance on DNA repair mechanisms.
  • Understanding the biofunctional categories of DNARi aids in developing targeted cancer therapies.
  • Future research should focus on novel DNARi and their clinical translation for improved patient outcomes.
Keywords:
DNA damage repairDNA damage responsegenomic instabilityhomologous recombination defectsmutational burdensynthetic lethality

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