On the contrary, mTOR and NOTCH inhibitors (e.g., rapamycin and DAPT) reduce the CD133+/EpCAM+ enrichment of both the epithelial and mesenchymal-like HCC cells, showing that rapamycin prior to sorafenib administration is the best option able to reduce the formation of tumor spheres. This evidence concerns the gene PROM1 and hepatocellular carcinoma.