Abstract: The disclosure provides methods and compositions for increasing sensitivity, or decreasing resistance, of cancer cells to chemotherapeutic agents such as kinase inhibitor agents. In some embodiments, the cancer cells are hepatocellular carcinoma (HCC) cells. The methods and compositions can be integrated into methods of treatment of a subject with cancer, which can further comprise administering a chemotherapeutic agent such as kinase inhibitor agents. In another aspect, the disclosure provides a method for profiling the kinome of a cell or group of similar cells that incorporates kinase capture reagents and mass spectrometry analysis.