Department of Gastroenterology, Hepatology, & Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Expert Opin Ther Targets. 2013 Jul;17(7):743-60. doi: 10.1517/14728222.2013.782287. Epub 2013 May 7.
The transforming growth factor-β (TGF-β) signaling pathway has a pivotal role in tumor suppression and yet, paradoxically, in tumor promotion. Functional context dependent insights into the TGF-β pathway are crucial in developing TGF-β-based therapeutics for cancer.
This review discusses the molecular mechanism of the TGF-β pathway and describes the different ways of tumor suppression by TGF-β. It is then explained how tumors can evade these effects and how TGF-β contributes to further growing and spreading of some of the tumors. In the last part of the review, the data on targeting TGF-β pathway for cancer treatment is assessed. This review focuses on anti-TGF-β based treatment and other options targeting activated pathways in tumors where the TGF-β tumor suppressor pathway is lost. Pre-clinical as well up to date results of the most recent clinical trials are given.
Targeting the TGF-β pathway can be a promising direction in cancer treatment. However, several challenges still exist, the most important are differentiating between the carcinogenic effects of TGF-β and its other physiological roles, and delineating the tumor suppressive versus the tumor promoting roles of TGF-β in each specific tumor. Future studies are needed in order to find safer and more effective TGF-β-based drugs.
转化生长因子-β（TGF-β）信号通路在肿瘤抑制中具有关键作用，但矛盾的是，它在肿瘤促进中也发挥着作用。深入了解 TGF-β 通路的功能背景对于开发基于 TGF-β 的癌症治疗方法至关重要。
本文讨论了 TGF-β 通路的分子机制，并描述了 TGF-β 抑制肿瘤的不同方式。然后解释了肿瘤如何逃避这些效应，以及 TGF-β 如何促进部分肿瘤的进一步生长和扩散。在本文的最后一部分，评估了针对 TGF-β 通路治疗癌症的数据。本文重点关注基于抗 TGF-β 的治疗以及针对 TGF-β 肿瘤抑制途径丧失的肿瘤中激活途径的其他选择。本文提供了临床前和最新临床试验的最新结果。
靶向 TGF-β 通路可能是癌症治疗的一个有前途的方向。然而，仍然存在一些挑战，最重要的是区分 TGF-β 的致癌作用与其其他生理作用，以及在每种特定肿瘤中区分 TGF-β 的肿瘤抑制作用与肿瘤促进作用。需要进一步研究以寻找更安全、更有效的基于 TGF-β 的药物。
