In sorafenib-resistant TC cell lines, sorafenib sensitivity was restored when combined with EZH2 inhibitor.435 Furthermore, sorafenib has been shown to induce apoptosis in HCC cells by accelerating the EZH2 degradation, suggesting that EZH2 inhibitors in combination with TKI reverses drug resistance and potentially enhances the drug efficacy before resistance.436 2,4-pyrimidinediamine derivative 10 f is a dual ALK and HDAC inhibitor. The gene discussed is EZH2; the disease is hepatocellular carcinoma.