Fig. 1

m⁶A-mediated biological processes of drug resistance. m⁶A was involved in several aspects of drug pharmacokinetics. m⁶A modifications upregulated drug transporters (e.g., ABCB1, ABCC1, ABCC10), facilitating ATP-driven drug efflux. m⁶A was also engaged in regulating several drug-metabolizing enzymes (e.g., CYP2C8 and UGT2B7) that affected the efficacy of chemotherapeutic drugs. Some drug targets (e.g., EGFR) were regulated by m⁶A and affected cancer development. Additionally, m⁶A also participated in activating downstream effects, which were embodied in the following three aspects. Firstly, m⁶A could selectively upregulate the p53 (R273 H) protein, releasing prohibited anti-apoptotic proteins (e.g., BCL-2, IAPs). Secondly, m⁶A altered the expression of various key signaling molecules (e.g., ULK1, FOXO3) in autophagy and ultimately regulated autophagy through light chain 3-II (LC3-II). Thirdly, m⁶A modification activated oncogenic bypass signaling through key molecules (e.g., IGF1R, DUXAP8) and promoted cell stemness, which became an important barrier to drug resistance. Immune cell infiltration and cytokine secretion in the tumor microenvironment were also regulated by m⁶A, which was relevant for cancer immunotherapy. The m⁶A modification of exosomal non-coding RNA was implicated in multiple biological processes in tumors and was associated with resistance to multiple anticancer drugs