Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The DNA damage response (DDR) is crucial for cancer progression and treatment efficacy.
• ATR (ataxia telangiectasia mutated and Rad3-related) kinase is a key regulator of the DDR pathway.
• Dysregulation of DDR pathways, particularly ATR, is implicated in various cancers.

Purpose of the Study:

• To review the biological basis and functional significance of ATR in cancer development and therapy.
• To evaluate the therapeutic rationale for targeting ATR in cancer treatment.
• To assess the progress in developing selective ATR inhibitors and their current applications.

Main Methods:

• Review of existing literature on ATR kinase and its role in DNA damage response.
• Analysis of preclinical and clinical studies involving ATR inhibitors.
• Examination of the development of selective ATR inhibitors over past decades.

Main Results:

• ATR inhibitors demonstrate anti-tumor activity as monotherapies and in combination regimens.
• ATR inhibition enhances the efficacy of chemotherapy, radiation, and immunotherapy.
• Development of effective and selective ATR inhibitors has progressed significantly.

Conclusions:

• ATR kinase represents a validated therapeutic target for cancer treatment.
• ATR inhibitors offer a promising strategy for monotherapy and combination therapies.
• Addressing identified challenges in ATR inhibitor development and application is crucial for clinical success.