Therapeutic Options Targeting the Ataxia-Telangiectasia Mutated (ATM)-mediated DNA Damage Response, Macropinocytosis, and Adaptive Immunity in Ovarian Cancer

Abstract

Ataxia-telangiectasia mutated (ATM) is a pivotal protein with versatile kinase activity that responds to DNA damage. While its well-established role as a DNA repair protein is widely recognized, the understanding of its noncanonical functions in ovarian cancer remains limited. Numerous studies have investigated the potential of targeting ATM for ovarian cancer treatment. In addition to its involvement in homologous recombination repair (HRR), an increasing body of research suggests that ATM plays a role in cellular metabolism and adaptive immunity. This review focuses on the current evidence and provides a perspective on how targeting ATM in ovarian cancer can address HRR-deficient genotypes, influence macropinocytosis, and enhance immune checkpoint blockade (ICB) therapy. It underscores the diverse avenues through which targeting ATM is a potential tailored treatment for ovarian cancer.

Keywords: ATM; DNA damage response; adaptive immunity; macropinocytosis; ovarian cancer; review.