Transforming growth factor-β (TGFβ)是一种具有癌症抑制和促进性质的多效分泌细胞因子。它通过抑制母亲反对十足腿(SMAD)和非SMAD途径传递其信号，调节细胞增殖、分化、侵入、迁移和凋亡。在非癌症和早期癌细胞中，TGFβ信号通过诱导细胞凋亡、细胞周期阻滞或抗增殖和促进细胞分化来抑制癌症进展。另一方面，在肿瘤的晚期阶段，TGFβ也可能作为一个癌基因，在那里它会形成免疫抑制性肿瘤微环境，并诱导癌细胞增殖、侵袭、血管生成、肿瘤形成和转移。更高的TGFβ表达会导致癌症的发生和发展。因此，抑制TGFβ信号可能是一种潜在的治疗选择，以抑制肿瘤形成和转移。已经开发和临床试验了不同的抑制分子，包括配体陷阱、反义寡核苷酸、小分子受体激酶抑制剂、小分子抑制剂和疫苗，用于阻断TGFβ信号通路。这些分子不是特异性的促癌反应，但可以阻止TGFβ诱导的所有信号效应。尽管如此，针对TGFβ信号的激活，使其具有最大化的特异性和最小化的毒性，可以提高针对该信号通路的治疗方法的疗效。用于靶向TGFβ的分子对癌细胞无细胞毒性，但设计用于减轻基质和癌细胞中TGFβ信号的过度激活驱动的侵袭和转移。在这里，我们讨论了TGFβ在肿瘤形成和转移中的关键作用，以及在癌症治疗中TGFβ抑制分子的成果和前景。版权所有©2023 Elsevier B.V.出版。

Transforming growth factor-β (TGFβ) is a pleiotropic secretory cytokine exhibiting both cancer-inhibitory and promoting properties. It transmits its signals via Suppressor of Mother against Decapentaplegic (SMAD) and non-SMAD pathways and regulates cell proliferation, differentiation, invasion, migration, and apoptosis. In non-cancer and early-stage cancer cells, TGFβ signaling suppresses cancer progression via inducing apoptosis, cell cycle arrest, or anti-proliferation, and promoting cell differentiation. On the other hand, TGFβ may also act as an oncogene in advanced stages of tumors, wherein it develops immune-suppressive tumor microenvironments and induces the proliferation of cancer cells, invasion, angiogenesis, tumorigenesis, and metastasis. Higher TGFβ expression leads to the instigation and development of cancer. Therefore, suppressing TGFβ signals may present a potential treatment option for inhibiting tumorigenesis and metastasis. Different inhibitory molecules, including ligand traps, anti-sense oligo-nucleotides, small molecule receptor-kinase inhibitors, small molecule inhibitors, and vaccines, have been developed and clinically trialed for blocking the TGFβ signaling pathway. These molecules are not pro-oncogenic response-specific but block all signaling effects induced by TGFβ. Nonetheless, targeting the activation of TGFβ signaling with maximized specificity and minimized toxicity can enhance the efficacy of therapeutic approaches against this signaling pathway. The molecules that are used to target TGFβ are non-cytotoxic to cancer cells but designed to curtail the over-activation of invasion and metastasis driving TGFβ signaling in stromal and cancer cells. Here, we discussed the critical role of TGFβ in tumorigenesis, and metastasis, as well as the outcome and the promising achievement of TGFβ inhibitory molecules in the treatment of cancer.Copyright © 2023. Published by Elsevier B.V.