Department of Pharmacology, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, J1H 5N4, Canada.
Target Oncol. 2015 Mar;10(1):1-14. doi: 10.1007/s11523-014-0308-y. Epub 2014 Mar 5.
Malignant gliomas are the most common type of primary malignant brain tumors. They are characterized by enhanced growing capabilities, neoangiogenic proliferation, and extensive infiltration of the brain parenchyma, which make their complete surgical resection impossible. Together with transient and refractory responses to standard therapy, these aggressive neoplasms are incurable and present a median survival of 12 to 14 months. Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine of which two of the three isoforms expressed in humans have been shown to be overexpressed proportionally to the histologic grade of glioma malignancy. The increase of chromosomal aberrations and genetic mutations observed in glioma cells turns TGF-β into an oncogene. For that reason, it plays critical roles in glioma progression through induction of several genes implicated in many carcinogenic processes such as proliferation, angiogenesis, and invasion. Consequently, investigators have begun developing innovative therapeutics targeting this growth factor or its signaling pathway in an attempt to hinder TGF-β's appalling effects in order to refine the treatment of malignant gliomas and improve their prognosis. In this paper, we extensively review the TGF-β-induced oncogenic pathways and discuss the diverse new molecules targeting this growth factor.
恶性胶质瘤是最常见的原发性恶性脑肿瘤。它们的特征是生长能力增强、新生血管增殖和广泛浸润脑实质，这使得完全手术切除成为不可能。加上对标准治疗的短暂和难治性反应，这些侵袭性肿瘤是无法治愈的，中位生存期为 12 到 14 个月。转化生长因子-β（TGF-β）是一种多功能细胞因子，其中人类表达的三种同工型中的两种被证明与胶质瘤恶性程度成正比过度表达。在胶质瘤细胞中观察到的染色体畸变和基因突变的增加使 TGF-β 成为一种癌基因。因此，它通过诱导许多致癌过程中涉及的几个基因（如增殖、血管生成和侵袭），在胶质瘤的进展中发挥关键作用。因此，研究人员已经开始开发针对这种生长因子或其信号通路的创新疗法，试图阻止 TGF-β 的可怕影响，以改善恶性胶质瘤的治疗并改善其预后。在本文中，我们广泛综述了 TGF-β 诱导的致癌途径，并讨论了针对这种生长因子的多种新分子。
