The protein arginine methyltransferase 5 (PRMT5) as the major type II arginine methyltransferase catalyzes the mono- and symmetric dimethylation of arginine residues in both histone and non-histone proteins. Recently, increasing evidence has demonstrated that PRMT5 plays an indispensable role in the occurrence and development of various human cancers by promoting the cell proliferation, invasion, and migration. It has become a promising and valuable target in the cancer epigenetic therapy. This review is to summarize the clinical significance of PRMT5 in the cancers such as lung cancer, breast cancer and colorectal cancer, and the drug discovery targeting PRMT5. Importantly, the existing PRMT5 inhibitors representing different molecular mechanisms, and their pharmacological effect, mechanism of action and biological affinity are analyzed. Clinical status, current problems and future perspective of PRMT5 inhibitors for the treatment of cancers are also discussed, all of which provides crucial help for the future discovery of PRMT5 targeted drugs for cancer treatment.

In this review, the pioneering progress of pharmacological mechanism, clinical significance and drug discovery of PRMT5 in the cancers was summarized.