FOXO3 and cancer: The deletion of METTL3 inhibits the m6A modification of FOXO3 mRNA via YTHDF1, thereby facilitating sorafenib resistance and cancer proliferation in HCC.238 Inhibiting the demethylase activity of FTO with Rhein can sensitize resistant cells to TKIs, downregulate Bcl-2 and MER proto-oncogene, tyrosine kinase (MERTK), thus regulating the PI3K-AKT-mTOR pathway and the Bcl-2 family of proteins, which affects the invasion and apoptosis of cancer cells.691–693 Therefore, the FTO-m6A axis has become a new indicator for TKI resistance.