BMPs as therapeutic targets and biomarkers in astrocytic glioma

Abstract

Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC) fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

Figure 1

(a) Glioma initiating cells seem to be radioresistant and chemoresistant to conventional therapies and, eventually, this results in tumor recurrence. (b) One approach to target GICs in GBM could be to develop a specific chemotherapeutic agent (such as BMPs or newly synthesized molecules mimicking BMPs) able to induce GICs to differentiate into cells more amenable to standard therapy. The expression of BMPRIB would be key for inducing differentiation of GICs.