Understanding Glioblastoma Signaling, Heterogeneity, Invasiveness, and Drug Delivery Barriers

Abstract

The most prevalent and aggressive type of brain cancer, namely, glioblastoma (GBM), is characterized by intra- and inter-tumor heterogeneity and strong spreading capacity, which makes treatment ineffective. A true therapeutic answer is still in its infancy despite various studies that have made significant progress toward understanding the mechanisms behind GBM recurrence and its resistance. The primary causes of GBM recurrence are attributed to the heterogeneity and diffusive nature; therefore, monitoring the tumor’s heterogeneity and spreading may offer a set of therapeutic targets that could improve the clinical management of GBM and prevent tumor relapse. Additionally, the blood–brain barrier (BBB)-related poor drug delivery that prevents effective drug concentrations within the tumor is discussed. With a primary emphasis on signaling heterogeneity, tumor infiltration, and computational modeling of GBM, this review covers typical therapeutic difficulties and factors contributing to drug resistance development and discusses potential therapeutic approaches.

New Insights into Glioblastoma

“…Another factor involved in GBM treatment failure is the blood-brain barrier (BBB), which is an obstacle in delivering optimal concentrations of anti-tumor drugs [5]. The use of devices emitting low-intensity pulsed ultrasound waves with the concomitant administration of intravenous microbubbles (LIPU-MB) is under investigation in order to evaluate its emerging role in opening the BBB.…”