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![Innate and adaptive resistance mechanisms to arginine deprivation therapies in sarcoma and other cancers](https://image.oaes.cc/21153ed9-f381-4269-ae7f-11b813a9a554/3194.fig.2.jpg)
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