ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment
Mateusz Kciuk1, Renata Gruszka1, Marta Aleksandrowicz2
1Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland.
International Journal of Molecular Sciences
|August 28, 2025
Summary
ATR-CHK1 inhibitors show promise for treating gastric cancer by targeting DNA damage response pathways. This approach offers new therapeutic strategies for patients with advanced disease, especially when combined with other treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Gastric cancer presents a significant global health burden with poor prognosis for advanced cases.
- Tumors exhibit vulnerabilities in DNA damage response (DDR) pathways, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and replication stress.
- These vulnerabilities create a dependency on the ATR-CHK1 axis for cancer cell survival.
Purpose of the Study:
- To review current clinical and preclinical evidence for ATR and CHK1 inhibitors in gastric cancer treatment.
- To explore the potential of these inhibitors based on synthetic lethality and immune modulation.
- To discuss resistance mechanisms and strategies for overcoming therapeutic failure.
Main Methods:
- Synthesis of existing clinical and preclinical data on ATR/CHK1 inhibitors.
- Analysis of molecular vulnerabilities in gastric cancer, focusing on DDR pathways.
- Review of combination strategies involving chemotherapy, radiotherapy, and immunotherapy.
Main Results:
- ATR-CHK1 axis inhibition represents a promising therapeutic strategy for gastric cancer.
- Combination regimens with chemotherapy, radiotherapy, or immune checkpoint inhibitors may enhance efficacy.
- Biomarker-guided selection and adaptive dosing are crucial for optimizing treatment precision and reducing toxicity.
Conclusions:
- ATR-CHK1 inhibitors offer a rational approach for treating specific gastric cancer subsets.
- Understanding resistance mechanisms is key to developing effective therapeutic strategies.
- Further research and clinical integration of these inhibitors are warranted for biomarker-defined patient populations.
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