fig2

Figure 2. Common Pathway of Resistance to ADI-PEG20. Arginine deprivation caused by ADI-PEG20 inhibits mTORC1, resulting in a decrease of repressive HIF-1α activity. By separate pathways, the positive transcription factor c-Myc is upregulated and causes increased ASS1 transcription and translation. ADI-PEG20 treatment also increases citrulline levels, which the cell can convert to arginine after ASS1 re-expression, resulting in resistance and the ability to proliferate. ADI-PEG20: PEGylated arginine deiminase; ASS1: argininosuccinate synthetase 1; mTOR: mammalian target of rapamycin