Recent advances in ATM inhibitors as potential therapeutic agents
Chao Dong1, Yong Wang1, Zhenlin Tu1
1School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, PR China.
Abstract:
ATM, a member of the PIKK-like protein family, plays a central role in responding to DNA double-strand breaks and other lesions to protect the genome against DNA damage. Loss of ATM's kinase function has been shown to increase the sensitivity of most cells to ionizing radiation. Therefore, ATM is thought to be a promising target for chemotherapy as a radiotherapy sensitizer. The mechanism of ATM in cancer treatment and the development of its inhibitors have become research hotspots. Here we present an overview of research concerning ATM protein domains, functions and inhibitors, as well as perspectives and insights for future development of ATM-targeting agents.
Insights
Ataxia-telangiectasia mutated (ATM) protein is crucial for DNA repair and genome stability. Targeting ATM offers a promising strategy to enhance cancer radiotherapy effectiveness.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Ataxia-telangiectasia mutated (ATM) is a key protein kinase involved in DNA damage response.
- ATM deficiency increases cellular sensitivity to ionizing radiation, suggesting its role in cancer therapy.
Purpose of the Study:
- To provide a comprehensive overview of ATM protein domains, functions, and inhibitors.
- To discuss the potential of ATM-targeting agents in cancer treatment, particularly as radiotherapy sensitizers.
Main Methods:
- Literature review of research on ATM protein.
- Analysis of ATM's role in DNA repair pathways.
- Review of current and emerging ATM inhibitors.
Main Results:
- ATM's critical role in DNA double-strand break repair and genome protection is highlighted.
- ATM's kinase function is essential for cellular resistance to DNA damage.
- Numerous ATM inhibitors are under investigation for cancer therapy.
Conclusions:
- ATM is a significant target for developing novel cancer therapies.
- Targeting ATM can enhance the efficacy of radiotherapy by sensitizing cancer cells.
- Further research into ATM inhibitors holds promise for future cancer treatment strategies.
