Therefore, in search for a rational combination with everolimus, we decided to choose a combination with a microtubule-targeting agent, patupilone, based on the following evidence: (1) microtubule-targeting is believed to be a prominent druggable target in HCC [15–17], more importantly, (2) dual targeting of mTOR and microtubule by temsirolimus and vinblastine has recently shown sustained and potent antitumor effect in HCC models [20], and, lastly, (3) patupilone has been reported to be the most potent microtubule-targeting agent for HCC [35]. Here, MTOR is linked to hepatocellular carcinoma.