A novel compound, SYHA1813, inhibits malignant meningioma growth directly by boosting p53 pathway activation and impairing DNA repair.

Abstract

Introduction: Meningioma is a common tumor of the central nervous system but effective therapies for malignant meningiomas are still lacking. Therefore, the development of novel therapeutic reagents is urgently needed. SYHA1813 is a novel compound and our previous study demonstrated its potent anti-tumor activity on glioblastoma through the inhibition of macrophages and human umbilical vein endothelial cells (HUVECs). However, the precise functional role of SYHA1813 in meningiomas remains unclear.

Method: We aimed to investigate the direct tumor-inhibitory effects of SYHA1813 on meningioma both in vitro and in vivo, and explore its potential molecular mechanisms.

Results: Our results showed that SYHA1813 suppressed the proliferation, colony formation, migration, and invasion of meningioma cells in vitro. Furthermore, we found SYHA1813 induced G2/M cell cycle arrest, apoptosis, and cellular senescence. Mechanistically, RNA-seq revealed that SYHA1813 activated the P53 pathway and impaired DNA repair. In vivo, SYHA1813 effectively inhibited the growth of meningioma xenografts in a mouse model. Additionally, in an ongoing first-inhuman phase I trial, this patient with recurrent meningioma provided preliminary clinical evidence supporting the anti-tumor activity of SYHA1813.

Discussion: This study unveiled a novel antitumor mechanism of SYHA1813, showing its ability to directly target and kill meningioma cells in vitro and in vivo. Our findings highlighted the promising potential of SYHA1813 as a therapeutic agent for treating malignant meningiomas.