Recent Advances in ATM Inhibitors As Potential Therapeutic Agents

Abstract

ATM, a member of the phosphatidylinositol-3-kinase-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.

Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors

“…Moreover, numerous proteins associated with DDR within the ATM-P53 pathway, as well as its downstream pathways, were significantly modulated, as depicted in Figure S1. Given the pivotal role of ATM in cancer initiation and progressions, 42 its identification as a potential target prompted us to proceed with further validation studies.…”

Interplay between altered metabolism and DNA damage and repair in ovarian cancer

“…For instance, ATM inhibitors are being tested in clinical trials. While pre‐clinical studies show a synergy between ATM inhibitors and DNA damaging agents, [ 158,159 ] we and others have shown that ATM has effects outside of the DDR. [ 146 ] Indeed, our recent study found that inhibition of ATM increases nutrient uptake and promotes survival of ovarian cancer.…”