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. Here, MTOR is linked to hepatocellular carcinoma.