Notch signaling in malignant gliomas: supporting tumor growth and the vascular environment

Abstract Glioblastoma is the most malignant form of glioma, which is the most commonly occurring tumor of the central nervous system. Notch signaling in glioblastoma is considered to be a marker of an undifferentiated tumor cell state, associated with tumor stem cells. Notch is also known for facilitating tumor dormancy escape, recurrence and progression after treatment. Studiesin vitro suggest that reducing, removing or blocking the expression of this gene triggers tumor cell differentiation, which shifts the phenotype away from stemness status and consequently facilitates treatment. In contrast, in the vasculature, Notch appears to also function as an important receptor that defines mature non-leaking vessels, and increasing its expression promotes tumor normalization in models of cancerin vivo. Failures in clinical trials with Notch inhibitors are potentially related to their opposing effects on  the tumor versus the tumor vasculature, which points to the need for a greater understanding of this signaling pathway.
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research