The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy

• Main Authors: Vincenzo Mattei, Francesca Santilli, Stefano Martellucci, Simona Delle Monache, Jessica Fabrizi, Alessandro Colapietro, Adriano Angelucci, Claudio Festuccia
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: International Journal of Molecular Sciences
• Subjects: glioblastoma; glioblastoma stem cells; cancer stem cells; glioblastoma therapy resistance; glioblastoma stem cells and therapy resistance; new drugs in the treatment of glioblastoma stem cells
• Online Access: https://www.mdpi.com/1422-0067/22/8/3863
• ISSN: 1661-6596; 1422-0067

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.