Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies.

Marta Cenciarini,Mario Valentino,Paolo Rosa,Maria Cristina D’Adamo,Simona Ronchetti,Silvia Belia,Luigi Sforna,Mauro Pessia

doi:10.3389/fnmol.2019.00065

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant of the glial tumors. The world-wide estimates of new cases and deaths annually are remarkable, making GBM a crucial public health issue. Despite the combination of radical surgery, radio and chemotherapy prognosis is extremely poor (median survival is approximately 1 year). Thus, current therapeutic interventions are highly unsatisfactory. For many years, GBM-induced brain oedema and inflammation have been widely treated with dexamethasone (DEX), a synthetic glucocorticoid (GC). A number of studies have reported that DEX also inhibits GBM cell proliferation and migration. Nevertheless, recent controversial results provided by different laboratories have challenged the widely accepted dogma concerning DEX therapy for GBM. Here, we have reviewed the main clinical features and genetic and epigenetic abnormalities underlying GBM. Finally, we analyzed current notions and concerns related to DEX effects on cerebral oedema, cancer cell proliferation and migration and clinical outcome.

Highlights

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, accounting for 54% of all gliomas (Dolecek et al, 2012)
GBM-induced cerebral oedema is currently treated with corticosteroids due to their ability to decrease the permeability of the blood brain barrier (BBB; Salvador et al, 2014)
As a resource for those interested in this issue, we have reviewed relevant critical articles from various research groups describing DEX actions in GBM and discussed proposed mechanisms and controversies

Summary

Introduction

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, accounting for 54% of all gliomas (Dolecek et al, 2012). The overall effects resulting from activation of these signaling pathways are increased cell proliferation and tumor growth. DEX did not influence the in vitro proliferation of GL261 cells, the decrease in tumor mass could be accounted for its effects on Ang-2 expression (Villeneuve et al, 2008).

Results

Conclusion