Mattei Vincenzo, Santilli Francesca, Martellucci Stefano, Delle Monache Simona, Fabrizi Jessica, Colapietro Alessandro, Angelucci Adriano, Festuccia Claudio
Biomedicine and Advanced Technologies Rieti Center, Sabina Universitas, 02100 Rieti, Italy.
Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy.
Int J Mol Sci. 2021 Apr 8;22(8):3863. doi: 10.3390/ijms22083863.
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.
胶质母细胞瘤（GBM）是已知最常见且致命的原发性恶性脑肿瘤。针对这种肿瘤的治疗失败率很高，这与自我更新的胶质母细胞瘤干细胞（GSCs）的存活有关，这些干细胞会使治疗后的肿瘤重新增殖。此外，尽管有新的根治性手术方案以及新抗癌药物的引入、治疗方案和放疗技术的进步，但GBM的生存率并未实现显著提高。因此，新型抗靶点疗法可与标准放化疗方法联合使用。事实上，靶向治疗可以针对在GBM细胞增殖、存活和侵袭中起关键作用的特定靶点，包括许多参与信号转导通路的分子。显著的细胞异质性以及GSCs表现出抗治疗表型的层级结构可以解释肿瘤复发和局部侵袭，因此可能成为新疗法的靶点。所以，GSCs的强制分化可能是GBM治疗中一种有前景的新方法。本文提供了GBM当前标准和实验性治疗方法的最新综述，以及GSCs分子特征、激活对当前治疗耐药机制的概述，还有一种用于治疗GSCs的新抗肿瘤策略以供治疗使用。
