Will EGFRvIII and neuronal-derived EGFR be targets for imipramine?

Frontiers in Pharmacology

Pharmacology

Jianjian Wu¹  Zesheng Li²  Bo Wang²  Lei Han² 

[1] Department of Environment, College of Environment and Resources, Xiangtan University, Xiangtan, China;Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, China;

关键词: glioblastoma;    tricyclic antidepressant (TCA);    cancer biology;    neuroscience < neuropharmacology;    translational medicine;    EGFR;   

DOI  :  10.3389/fphar.2023.1156492

 received in 2023-02-01, accepted in 2023-05-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

Tricyclic antidepressant is an old and well-established therapeutic agent with a good safety profile, making them an excellent candidate for repurposing. In light of the growing understanding of the importance of nerves in the development and progression of cancer, attention is now being turned to using nerve-targeting drugs for the treatment of cancer, particularly TCAs. However, the specific mechanism by which antidepressants affect the tumor microenvironment of glioblastoma (GBM) is still unclear. Here, we combined bulk RNA sequencing, network pharmacology, single-cell sequencing, molecular docking and molecular dynamics simulation to explore the potential molecular mechanism of imipramine in the treatment of GBM. We first revealed that the imipramine treatment is presumed to target EGFRvIII and neuronal-derived EGFR, which may play a pivotal role in treating GBM by reducing the GABAergic synapse and vesicle-mediated release and other processes thereby modulating immune function. The novel pharmacological mechanisms might provide further research directions.

【 授权许可】

Unknown   
Copyright © 2023 Li, Wang, Wu and Han.