Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand

Abstract

BackgroundThe ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase 1 (CHK1) pathway plays an essential role in suppressing replication stress from DNA damage and oncogene activation.Main bodyPreclinical studies have shown that cancer cells with defective DNA repair mechanisms or cell cycle checkpoints may be particularly sensitive to ATR inhibitors. Preclinical and clinical data from early-phase trials on three ATR inhibitors (M6620, AZD6738, and BAY1895344), either as monotherapy or in combination, were reviewed.ConclusionData from ATR inhibitor-based combinational trials might lead to future expansion of this therapy to homologous recombination repair pathway-proficient cancers and potentially serve as a rescue therapy for patients who have progressed through poly ADP-ribose polymerase inhibitors.