The focus will now shift to the specific mechanisms of mitogen‐activated protein kinase (MAPK), the cellular myelocytomatosis oncogene (c‐Myc), HIF‐1, the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and p53 in targeted drug resistance in HCC (Figure 3). Here, TP53 is linked to hepatocellular carcinoma.