ATR and cancer: Relevant to the present study and the sensitivity of the BRCA-defective cancers to DSF/CuET, we and others previously discovered enhanced replication stress and endogenous DNA damage as a candidate hallmark of cancer [7,8,9,10], thereby pioneering the concept of the ATM-Chk2- and ATR-Chk1-mediated DNA damage response (DDR) checkpoints as important cell-intrinsic barriers against oncogene activation and tumor progression [10,11,12].