Roles and drug development of METTL3 (methyltransferase-like 3) in anti-tumor therapy

Methyltransferase complex, such as METTL3/METTL14/WTP, catalyze N6-methyladenosine (m6A), which is the most abundant mRNA modification in mammals. Besides acting as a m6A methyltransferase, METTL3 also regulates mRNA translation and other biological processes. Studies have identified numerous roles and molecular mechanisms associated with METTL3 in multiple biological processes especially in tumors in recent years. Furthermore, targeting METTL3 as an efficient therapeutic way for the treatment of different kinds of tumors has gained a lot of attention. However, these findings and researches have not been summarized. In this review, the most recent important roles of METTL3 in various tumors including acute myeloid leukemia, lung cancer, breast cancer, liver cancer, gastric cancer, pancreatic cancer, colorectal cancer, bladder cancer, prostate cancer and glioblastoma were systematically summarized. In addition, disclosed METTL3 inhibitors recently were also summarized and discussed for medicinal chemists investigating METTL3 inhibitors with different skeleton structures for the application of human cancer therapy.