Targeting the TGF-beta1 pathway to prevent normal tissue injury after cancer therapy.
Targeting the TGF-beta1 pathway to prevent normal tissue injury after cancer therapy.
复制标题
DOI：
10.1634/theoncologist.2009-s101
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Anscher MS
中科院分区：
文献类型：
--
作者：
Anscher MS
本文综述了支持转化生长因子β1在肿瘤治疗后正常组织损伤发展中的关键作用的证据，并介绍了旨在通过靶向转化生长因子β1途径预防正常组织损伤的最新研究结果。仅在美国就有超过10，000，000名癌症幸存者，癌症治疗的晚期效应是一个重要的公共卫生问题。在过去的15年里，我们做了大量工作，提高了我们对癌症治疗后正常组织损伤发展的分子机制的理解。在许多情况下，这些损伤在组织学水平上以实质细胞损失、过度纤维化和组织萎缩为特征。在参与这一过程的许多细胞因子中，转化生长因子（TGF）-β1被认为起着关键作用。TGF-β1具有多种功能，包括促进结缔组织的形成和抑制结缔组织的破坏。它还抑制上皮细胞增殖。TGF-β1在放疗和化疗后的损伤部位过表达。因此，TGF-β1代表了设计用于预防或减少癌症治疗后正常组织损伤的分子治疗的逻辑靶标。本文综述了支持TGF-β 1在癌症治疗后正常组织损伤发展中的关键作用的证据，并介绍了最近旨在通过靶向TGF-β 1途径预防正常组织损伤的研究结果。
Evidence supporting the critical role of transforming growth factor β1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the transforming growth factor β1 pathway are presented. With >10,000,000 cancer survivors in the U.S. alone, the late effects of cancer treatment are a significant public health issue. Over the past 15 years, much work has been done that has led to an improvement in our understanding of the molecular mechanisms underlying the development of normal tissue injury after cancer therapy. In many cases, these injuries are characterized at the histologic level by loss of parenchymal cells, excessive fibrosis, and tissue atrophy. Among the many cytokines involved in this process, transforming growth factor (TGF)-β1 is thought to play a pivotal role. TGF-β1 has a multitude of functions, including both promoting the formation and inhibiting the breakdown of connective tissue. It also inhibits epithelial cell proliferation. TGF-β1 is overexpressed at sites of injury after radiation and chemotherapy. Thus, TGF-β1 represents a logical target for molecular therapies designed to prevent or reduce normal tissue injury after cancer therapy. Herein, the evidence supporting the critical role of TGF-ß1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the TGF-ß1 pathway are presented.