Proteoform-Based New Perspectives for Personalized Drug Therapy

Personalized medicine plays important roles in the field of pharmacy because it can enhance drug efficacy, improve the treatment effects, reduce adverse reactions, and optimize treatment outcomes. Protein drugs are an important part of personalized drug therapy with higher target specificity and biological activity compared to small molecule chemical drugs. Currently, protein drugs are designed and exploited for specific protein targets according to patient-specific protein data. However, with the rapid development of proteoform concept, a canonical protein actually includes multiple proteoforms encoded by the same gene, which can lead to different responses to drugs. The effects of the different proteoforms vary considerably, which may alter the intended efficacy of the drug to potentially render it harmful rather than lifesaving. Therefore, we strongly propose to shift protein-based drugs to proteoform-based drugs, which mean that, for the development of personalized protein drugs, we should pay more attention to the differences in proteoforms encoded by the same gene to better meet the specific needs and disease characteristics. Proteoform-based personalized drug therapy will help to accurately understand the mechanisms of diseases, discover new drug targets, and provide patients with more precisely individualized treatment, which is the innovative theoretical basis to develop new drugs.