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Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer

N J Curtin1

  • 1Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, UK. nicola.curtin@newcastle.ac.uk

British Journal of Pharmacology
|May 21, 2013
PubMed
Abstract

Insights

The DNA damage response (DDR) is crucial for cell survival and preventing cancer. Inhibitors targeting DDR pathways show promise in overcoming therapeutic resistance and treating specific tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The DNA damage response (DDR) network is essential for cell viability and genomic stability.
  • DDR pathways are frequently dysregulated in cancer, impacting treatment outcomes.
  • Understanding DDR alterations is key to developing novel cancer therapies.

Purpose of the Study:

  • To review compounds designed to inhibit specific DDR targets.
  • To summarize pre-clinical and clinical evaluations of DDR inhibitors.
  • To explore the therapeutic potential of DDR inhibitors in oncology.

Main Methods:

  • Literature review of DDR inhibitors.
  • Analysis of pre-clinical studies on DDR inhibitor efficacy.
  • Summary of clinical trial data for DDR-targeting agents.

Main Results:

  • Dysregulated DDR pathways in cancer can lead to therapeutic resistance.
  • Inhibitors of upregulated DDR pathways can overcome resistance to DNA damaging agents.
  • Targeting complementary DDR pathways in deficient tumors may induce selective cell killing.

Conclusions:

  • DDR inhibitors hold potential for increasing chemotherapy and radiotherapy efficacy.
  • These inhibitors may exhibit single-agent activity against tumors with specific DDR defects.
  • Targeted inhibition of DDR pathways represents a promising strategy in cancer treatment.
Keywords:
DNA damage signalling and repaircancersynthetic lethality

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