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Targeting the DNA-PK complex: Its rationale use in cancer and HIV-1 infection

C Schwartz1, O Rohr1, C Wallet1

  • 1University of Strasbourg, EA7292, DHPI, IUT Louis Pasteur, Schiltigheim, France.

Biochemical Pharmacology
|December 12, 2018
PubMed

Insights

The DNA-PK complex is crucial for DNA repair and impacts cancer and HIV-1. Targeting DNA-PK offers therapeutic potential for both diseases, but strategies must adapt to disease stage.

Area of Science:

  • Molecular Biology
  • Genetics
  • Virology

Background:

  • The DNA-PK complex is central to DNA double-strand break (DSB) repair in humans.
  • It also regulates DNA recombination, genome stability, apoptosis, and transcription.
  • Dysfunctional DNA-PK activity is implicated in cancer initiation and progression, and HIV-1 replication.

Purpose of the Study:

  • To review the dual role of the DNA-PK complex in cancer and HIV-1 infection.
  • To explore the rationale for targeting DNA-PK in these pathologies.
  • To discuss context-dependent therapeutic strategies for DNA-PK inhibition.

Main Methods:

  • Literature review of studies on DNA-PK function in cancer and HIV-1.
  • Analysis of the link between DNA-PK activity and disease progression.
  • Evaluation of therapeutic strategies targeting DNA-PK.

Main Results:

  • Decreased DNA-PK activity is linked to cancer initiation due to repair defects.
  • Elevated DNA-PK in tumors can reduce anti-cancer drug efficacy.
  • DNA-PK is essential for HIV-1 DNA integration and viral replication.

Conclusions:

  • Targeting the DNA-PK complex presents a viable therapeutic approach for both cancer and HIV-1.
  • Therapeutic strategies must be tailored based on disease status, such as cancer grade or HIV-1 replication.
  • Further research is needed to optimize context-specific DNA-PK inhibition therapies.
Keywords:
CancerDNA-PKDSB repairHIV-1Virus integration

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