Current status and prospects of methylthioadenosine phosphorylase/protein arginine methyltransferase 5 target therapy.

Methylthioadenosine phosphorylase (MTAP) and protein arginine methyltransferase 5 (PRMT5) are two important targets that have attracted much attention in oncology in recent years. The former is involved in methionine metabolism and its absence leads to accumulation of methylthioadenosine (MTA), an endogenous inhibitor of PRMT5, which is involved in cell cycle regulation, cell differentiation and deoxyribonucleic acid (DNA) repair by catalysing symmetrical dimethylation modification of arginine residues in proteins. Moreover, MTAP-depleted tumour cells are highly dependent on the remaining functions of PRMT5 and form synthetic lethal targets, providing new ideas for cancer therapy. This article reviews the importance of MTAP/PRMT5 targets in cancer therapy and their current research status. While PRMT5 inhibitors have shown promising anti-tumour activity in MTAP-null tumour models, providing novel therapeutic options for refractory cancers, therapies targeting MTAP/PRMT5 still face challenges, such as off-target toxicity, normal tissue toxicity and intratumoral heterogeneity. Future studies are needed to further optimise drug design, explore combination regimens and examine biomarkers to achieve precision medicine and improve patient outcomes and survival.