ADI-PEG 20 + sorafenib

**ADI-PEG 20 + sorafenib** is a combination therapy used experimentally in advanced hepatocellular carcinoma (HCC). ADI-PEG 20 is a PEGylated recombinant protein that enzymatically depletes arginine, an amino acid essential for the survival of some tumor cells, especially those deficient in argininosuccinate synthase 1 (ASS1). Arginine depletion interferes with pyrimidine metabolism and DNA repair pathways, starving cancer cells and impeding proliferation. Sorafenib is a small molecule kinase inhibitor that targets multiple receptor tyrosine kinases involved in tumor cell proliferation and angiogenesis, notably vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptor (PDGFR), and RAF kinases. This combination aims to exploit distinct mechanisms—metabolic deprivation by ADI-PEG 20 and kinase inhibition by sorafenib—to synergistically suppress cancer growth. This regimen is currently being evaluated in clinical studies, and initial results in phase 1 trials show acceptable tolerability, with the goal of improving treatment options for advanced HCC, an area of significant unmet medical need[1].

Other names

PEGylated arginine deiminase + sorafenib