Hepatocellular carcinoma and multidrug resistance: Past, present and new challenges for therapy improvement

Figure 2 Proposed mechanisms by which upregulation of hypoxia-inducible factor-2α induced by sorafenib contributes to the resistance by activating the transforming growth factor-α/epidermal growth factor receptors pathway in hepatocellular carcinoma cells. ARNT: Aryl hydrocarbon receptor nuclear translocator; EGFR: Epidermal growth factor receptor; ERK: Extracellular signal-regulated kinase; HIF-1α: Hypoxia-inducible factor-1α; HIF-2α: Hypoxia-inducible factor-2α; PHD: Prolyl hydroxylase; STAT3: Signal transducer and activator of transcription 3; TGF-α: Transforming growth factor-α; VEGF: Vascular endothelial growth factor; VEGFR: Vascular endothelial growth factor receptor. Reprinted from ref. [100] with permission from Elsevier.