Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands.
Biochem Pharmacol. 2013 Feb 15;85(4):478-85. doi: 10.1016/j.bcp.2012.11.005. Epub 2012 Nov 14.
Transforming growth factor-β (TGF-β) is a cytokine with a key role in tissue homeostasis and cancer. TGF-β elicits both tumor suppressive and tumor promoting functions during cancer progression, in a wide range of cancers. Here, we review the tumor promoting function of TGF-β and its possible promise as a therapeutic target in high grade gliomas, including glioblastoma multiforme (GBM), a disease with very poor prognosis. TGF-β signaling is highly active in high grade gliomas and elevated TGF-β activity has been associated with poor clinical outcome in this deadly disease. Common features of GBMs include fast cell proliferation, invasion into normal brain parenchyma, hypoxia, high angiogenic - and immunosuppressive activity, characteristics that all have been linked to activation of the TGF-β pathway. TGF-β signaling has also been connected with the cancer stem cell (CSC) phenotype in GBM. CSCs represent a subset of GBM cells thought to be responsible for tumor initiation, progression and relapse of disease. Following the description of these different properties of TGF-β signaling and the underlying mechanisms identified thus far, the promise of TGF-β targeted therapy in malignant gliomas is discussed. Several drugs targeting TGF-β signaling have been developed that showed potent antitumor activity in preclinical models. A number of agents are currently evaluated in early clinical studies in glioma patients. Available results of these studies are highlighted and a perspective on the promise of TGF-β-targeted therapy is given.
转化生长因子-β（TGF-β）是一种细胞因子，在组织稳态和癌症中具有关键作用。TGF-β在癌症进展过程中发挥着肿瘤抑制和促进肿瘤的作用，在多种癌症中均有体现。在这里，我们将回顾 TGF-β 的促进肿瘤作用及其在高级别神经胶质瘤（包括胶质母细胞瘤，GBM）中的潜在治疗靶点的意义，GBM 是一种预后极差的疾病。TGF-β 信号在高级别神经胶质瘤中高度活跃，TGF-β 活性升高与该致命疾病的临床预后不良相关。GBM 的常见特征包括细胞快速增殖、浸润正常脑实质、缺氧、高度血管生成和免疫抑制活性，这些特征都与 TGF-β 通路的激活有关。TGF-β 信号还与 GBM 中的癌症干细胞（CSC）表型有关。CSC 是 GBM 细胞的一个子集，被认为是肿瘤起始、进展和疾病复发的原因。在描述了 TGF-β 信号的这些不同特性及其迄今为止确定的潜在机制之后，我们将讨论 TGF-β 靶向治疗在恶性神经胶质瘤中的应用前景。已经开发出几种针对 TGF-β 信号的药物，这些药物在临床前模型中显示出强大的抗肿瘤活性。目前有许多药物正在 GBM 患者的早期临床试验中进行评估。本文强调了这些研究的结果，并对 TGF-β 靶向治疗的前景进行了展望。
