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Targeting ATM and ATR for cancer therapeutics: Inhibitors in clinic

Bhanu Priya1, Srimadhavi Ravi2, Sivapriya Kirubakaran2

  • 1Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj Campus, Gujarat 382355, India.

Drug Discovery Today
|June 11, 2023
PubMed

Insights

The DNA Damage and Response pathway is crucial for preventing cancer. Targeting ATM and ATR kinases, which repair DNA double-strand breaks (DSB), shows promise for cancer therapy.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • The DNA Damage and Response (DDR) pathway maintains genomic stability across generations.
  • Dysregulation of DDR is linked to cancer development, progression, and treatment outcomes.
  • DNA double-strand breaks (DSBs) are severe DNA lesions causing chromosomal abnormalities.

Purpose of the Study:

  • To review the roles of ATM and ATR kinases in DNA damage and repair.
  • To discuss challenges in targeting these kinases for cancer therapy.
  • To highlight inhibitors of ATM and ATR in clinical trials.

Main Methods:

  • Literature review of DNA damage and repair pathways.
  • Analysis of ATM and ATR kinase functions in cancer.
  • Survey of current clinical trials for ATM and ATR inhibitors.

Main Results:

  • ATM and ATR kinases are key sensors of DNA DSBs, initiating cellular responses.
  • Cancer cells exhibit a high reliance on DSB repair for survival.
  • Targeting ATM and ATR can sensitize cancer cells to DNA-damaging agents.

Conclusions:

  • ATM and ATR are critical for managing DNA DSBs and maintaining cancer cell viability.
  • Inhibitors targeting ATM and ATR present a promising therapeutic strategy in oncology.
  • Further research and clinical trials are essential to optimize ATM and ATR-targeted therapies.
Keywords:
DNA damage and repairataxia telangiectasia and Rad3 related kinaseataxia telangiectasia mutated kinasedouble-stranded breakshomologous recombinationinhibitors

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