Advances in treatment of immune-related adverse reactions and hyperprogressive diseases associated with antitumor immunotherapy with PD-1/PD-L1 monoclonal antibody drugs / 中国药理学与毒理学杂志

There have been breakthroughs in the development and clinical application of immuno-therapeutic agents in recent years.As the clinical targets of second-generation immune checkpoint inhibitors(ICIs),programmed death-1(PD-1)and its ligand(programmed death-ligand 1,PD-L1)have become one of the hot spots in drug discovery.The Food and Drug Administration of the USA and National Medical Products Administration in China have approved a variety of PD-1/PD-L1 monoclonal antibody drugs(such as nivolumab,pembrolizumab and atezolizumab),which are marketed for the treatment of small-cell lung cancer,rectal cancer,colon cancer,and melanoma,among other diseases.However,in the clinical application of PD-1/PD-L1 monoclonal antibody drugs,it is found that they can cause different degrees of immune-related adverse reactions in the lung,liver,kidney,gastrointestinal system,endocrine system and skin,and even the emergence of hyperprogressive disease.Effective monitoring and management of clinical applications of PD-1/PD-L1 monoclonal antibody drugs and rational use of some drugs can improve the immunotherapy process and reduce the effects of adverse reactions and hyperprogressive diseases in patients under immunotherapy.

-Methyladenosine modification: a novel pharmacological target for anti-cancer drug development

-Methyladenosine (mA) modification is the most pervasive modification of human mRNA molecules. It is reversible regulation of mA modification methyltransferase, demethylase and proteins that preferentially recognize mA modification as "writers", "erasers" and "readers", respectively. Altered expression levels of the mA modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the mA modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of mA modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key mA modification regulators for cancer drug development.