HIF1A and cancer: Given the recent discoveries that c-Myc and HIF-1α are involved in the regulation of cancer energy metabolism [40,41] (Fig. 1), our finding that c-Myc and HIF-1α have opposite responses to ADI-PEG20 treatment has important implications beyond the induction of ASS and ADI-PEG20 sensitivity, it underscores the global effects on cancer cell energy metabolism as well.