Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, accounting for 54% of all gliomas (Dolecek et al., 2012). The estimated number of annual new cases of GBM are: Japan 2,200, UK 2,531, France 3,000, Germany 3,500, USA 18,000. Globally, over 100,000 patients die each year as a result of this type of brain cancer. It is highly invasive and not amenable to current treatment such as surgical management, chemo- and radio-therapy (Furnari et al., 2007) and affected individuals have very poor life expectancy (Miller and Perry, 2007). The highly aggressive course and poor response to treatments likely result from uncontrolled cellular proliferation, migration, presence of a cancer stem-like cell population, neo-angiogenesis and severe brain oedema. 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). Dexamethasone (DEX) represents the drug of choice among the synthetic glucocorticoids (GCs) by virtue of its minimal mineralocorticoid activity, long half-life and high potency (Kostaras et al., 2014). By evaluating the typical features of GBM aggressiveness, several studies have shown positive effects of DEX on GBM cells both in vitro and cancer volume, in vivo (Guerin et al., 1992; Wolff et al., 1997; Kaup et al., 2001; Villeneuve et al., 2008; Piette et al., 2009; Fan et al., 2014) although, the mechanisms accounting for these actions remain unclear. Strikingly, contradictory evidence has been published generating controversies that are still debated. 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.

Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

Maria Cristina D’Adamo;
2019

Abstract

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, accounting for 54% of all gliomas (Dolecek et al., 2012). The estimated number of annual new cases of GBM are: Japan 2,200, UK 2,531, France 3,000, Germany 3,500, USA 18,000. Globally, over 100,000 patients die each year as a result of this type of brain cancer. It is highly invasive and not amenable to current treatment such as surgical management, chemo- and radio-therapy (Furnari et al., 2007) and affected individuals have very poor life expectancy (Miller and Perry, 2007). The highly aggressive course and poor response to treatments likely result from uncontrolled cellular proliferation, migration, presence of a cancer stem-like cell population, neo-angiogenesis and severe brain oedema. 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). Dexamethasone (DEX) represents the drug of choice among the synthetic glucocorticoids (GCs) by virtue of its minimal mineralocorticoid activity, long half-life and high potency (Kostaras et al., 2014). By evaluating the typical features of GBM aggressiveness, several studies have shown positive effects of DEX on GBM cells both in vitro and cancer volume, in vivo (Guerin et al., 1992; Wolff et al., 1997; Kaup et al., 2001; Villeneuve et al., 2008; Piette et al., 2009; Fan et al., 2014) although, the mechanisms accounting for these actions remain unclear. Strikingly, contradictory evidence has been published generating controversies that are still debated. 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12572/7773
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