ATR and cancer: In many cancer cells, the expression of ATM/ATR is downregulated164 and the activity of ATM/ATR is also reduced by upregulating WIP1 phosphatase, which dephosphorylates ATM/ATR and its substrates, e.g., p53.165 Interestingly, in certain types of cancers, where ATM/ATR is uncoupled from cell-cycle arrest and apoptosis, the overexpression of ATM/ATR has been found in many studies, which proves the importance of ATM/ATR in chemoresistance.166