Targeting DNA-Dependent Protein Kinase for Cancer Therapy

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Suzannah J Harnor1, Alfie Brennan1, Céline Cano1

  • 1Northern Institute for Cancer Research, Newcastle University, School of Chemistry, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK.

Chemmedchem
|April 20, 2017
PubMed

Insights

DNA-dependent protein kinase (DNA-PK) is crucial for repairing DNA double-strand breaks (DSBs). Inhibitors targeting DNA-PK are being developed to enhance cancer therapy effectiveness.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • DNA-dependent protein kinase (DNA-PK) plays a vital role in repairing lethal DNA double-strand breaks (DSBs).
  • DSBs can arise from oxidative stress, oncogene activity, or cancer treatments.
  • Targeting DNA-PK is a strategy to sensitize tumors to chemotherapy and radiotherapy.

Purpose of the Study:

  • To review the structures of known reversible and irreversible small-molecule inhibitors of DNA-PK.
  • To discuss the therapeutic potential of DNA-PK inhibitors in cancer treatment.

Main Methods:

  • Examination of chemical structures of DNA-PK inhibitors.
  • Review of existing literature on DNA-PK inhibitor development.
  • Analysis of clinical trial progress for specific inhibitors.

Main Results:

  • Identified inhibitors based on chromen-4-one, arylmorpholine, and benzaldehyde scaffolds.
  • Highlighted specific DNA-PK catalytic inhibitors, VX-984 and M3814, in clinical development.

Conclusions:

  • Small-molecule inhibitors of DNA-PK are progressing into clinical trials.
  • Further research is needed to determine the efficacy of DNA-PK inhibition as a cancer therapeutic strategy.
Keywords:
DNA damage responseDNA-PKchemopotentiationinhibitorskinases

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