Impact of mtCB1 signaling on glioblastoma progression

Glioblastoma, the most common and aggressive brain tumor in adults, is characterized by a high rate of recurrence and resistance to standard treatments, limiting the median survival of patients to around 15 months. These therapeutic challenges are largely due to the infiltrative nature of the tumor, its complex microenvironment, and metabolic alterations that promote tumor cell proliferation and disease progression.Cannabinoid receptors, particularly CB1, play a key role in regulating essential metabolic functions, especially within mitochondria, where they influence energy production, oxidative stress, and intracellular signaling. Preclinical studies have shown promising antitumor effects of these receptors, such as apoptosis induction, modulation of angiogenesis, and inhibition of tumor cell invasiveness. These studies also suggest that CB1 activation could specifically target resistant tumor stem cells, thereby reducing the risk of recurrence.

This project, conducted within the Tumoral and Vascular Biology Team at the Bordeaux Institute of oncology, aims to investigate the impact of cannabinoids on the energy metabolism of glioblastoma cells and their interactions with the tumor microenvironment. We will examine the effects of cannabinoid agonists and antagonists on oxygen consumption, ATP production, and mitochondrial dynamics in cell lines that either express or do not express the CB1 receptor. In addition, the study will explore how cannabinoids influence the interactions between glioblastoma cells and key components of the tumor microenvironment, such as fibroblasts and immune cells. Situated at the intersection of neuroscience and neuro-oncology, this research aims to deepen our understanding of the metabolic and environmental mechanisms driving glioblastoma progression. The results could open the door to novel therapeutic strategies that combine cannabinoids with existing treatments, with the goal of reducing tumor aggressiveness, limiting recurrences, and improving patient outcomes.

#Glioblastoma #Tumor microenvironment #Cannabinoid receptor #Metabolism #Mitochondrial respiration

Impact of mtCB1 signaling on glioblastoma progression

Glioblastoma, the most common and aggressive brain tumor in adults, is characterized by a high rate of recurrence and resistance to standard treatments, limiting the median survival of patients to around 15 months. These therapeutic challenges are largely due to the infiltrative nature of the tumor, its complex microenvironment, and metabolic alterations that promote tumor cell proliferation and disease progression.Cannabinoid receptors, particularly CB1, play a key role in regulating essential metabolic functions, especially within mitochondria, where they influence energy production, oxidative stress, and intracellular signaling. Preclinical studies have shown promising antitumor effects of these receptors, such as apoptosis induction, modulation of angiogenesis, and inhibition of tumor cell invasiveness. These studies also suggest that CB1 activation could specifically target resistant tumor stem cells, thereby reducing the risk of recurrence.

This project, conducted within the Tumoral and Vascular Biology Team at the Bordeaux Institute of oncology, aims to investigate the impact of cannabinoids on the energy metabolism of glioblastoma cells and their interactions with the tumor microenvironment. We will examine the effects of cannabinoid agonists and antagonists on oxygen consumption, ATP production, and mitochondrial dynamics in cell lines that either express or do not express the CB1 receptor. In addition, the study will explore how cannabinoids influence the interactions between glioblastoma cells and key components of the tumor microenvironment, such as fibroblasts and immune cells. Situated at the intersection of neuroscience and neuro-oncology, this research aims to deepen our understanding of the metabolic and environmental mechanisms driving glioblastoma progression. The results could open the door to novel therapeutic strategies that combine cannabinoids with existing treatments, with the goal of reducing tumor aggressiveness, limiting recurrences, and improving patient outcomes.

#Glioblastoma #Tumor microenvironment #Cannabinoid receptor #Metabolism #Mitochondrial respiration

internship supervisor

Antonio PAGANO ZOTTOLA