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Targeting DNA-PK in cancer

Giovanna Damia1

  • 1Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy.

Mutation Research
|March 16, 2020
PubMed

Insights

DNA-dependent protein kinase (DNA-PK) is crucial for DNA repair and genomic stability. Inhibiting DNA-PK offers a promising therapeutic strategy for cancer, particularly when combined with DNA-damaging agents.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • DNA-dependent protein kinase (DNA-PK) plays a vital role in cellular DNA damage response and repair.
  • It is essential for maintaining genomic integrity and involved in transcription, immune system development, and telomere protection.
  • Dysregulated DNA-PK expression is observed in various cancers, highlighting its significance in tumor biology.

Purpose of the Study:

  • To review the multifaceted roles of DNA-PK in cellular processes.
  • To explore the involvement of DNA-PK in tumor biology and DNA repair mechanisms.
  • To critically evaluate the therapeutic potential of DNA-PK inhibition in cancer treatment.

Main Methods:

  • Literature review of existing research on DNA-PK.
  • Analysis of DNA-PK's function in DNA double-strand break (DNA-DSB) repair.
  • Discussion of small molecule inhibitors and clinical trial data.

Main Results:

  • DNA-PK is a key regulator of DNA-DSB repair pathways.
  • Its inhibition can sensitize cancer cells to DNA-damaging therapies.
  • Several small molecule DNA-PK inhibitors are under clinical investigation.

Conclusions:

  • DNA-PK is a significant therapeutic target in oncology.
  • Targeting DNA-PK, especially in combination therapies, shows promise for cancer treatment.
  • Further research into DNA-PK inhibition is warranted to optimize its clinical application.
Keywords:
CancerDNA repairDNA-PKSmall molecule inhibitor

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