Calone I, Souchelnytskyi S
Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institute, Stockholm, Sweden.
Exp Oncol. 2012;34(1):9-16.
The transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis. In cancer, two distinctive behaviors of TGFβ have been reported as a tumor suppressor at early stage of the disease, and as a tumor promoter at later stages. The past decades, the dualistic role of TGFβ has garnered a lot of attention. As a result, cancer researchers' has been tasked to elucidate how TGFβ signaling may lead to metastatic dissemination, how to tackle carcinogenesis and which therapeutic strategies should be adopted. Consequently, TGFβ signaling pathways have been considered as appropriate targets for cancer therapy. The TGFβ therapeutic strategies have emerged at three levels: ligand, ligand-receptor interaction and intracellular signaling level. Promising inhibitors of TGFβ signaling have entered clinical trials and shown encouraging results. Here we review the three strategies of TGFβ signa-ling inhibition and theirs applications in treatment of cancer.
转化生长因子-β(TGFβ)是肿瘤发生的一种有效调节因子。在癌症中,TGFβ有两种不同的作用:在疾病早期作为肿瘤抑制因子,在疾病后期作为肿瘤促进因子。在过去几十年里,TGFβ的双重作用引起了广泛关注。因此,癌症研究人员的任务是阐明TGFβ信号传导如何导致转移扩散、如何应对致癌作用以及应采用哪些治疗策略。因此,TGFβ信号通路被认为是癌症治疗的合适靶点。TGFβ治疗策略已在三个层面出现:配体、配体-受体相互作用和细胞内信号传导层面。有前景的TGFβ信号抑制剂已进入临床试验并显示出令人鼓舞的结果。在此,我们综述TGFβ信号抑制的三种策略及其在癌症治疗中的应用。