Targeting TGFβ signal transduction for cancer therapy.
Targeting TGFβ signal transduction for cancer therapy.
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DOI：
10.1038/s41392-020-00436-9
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发表时间：
2021-01-08
影响因子：
39.3
通讯作者：
Ten Dijke P
中科院分区：
文献类型：
--
作者：
Liu S;Ren J;Ten Dijke P
转化生长因子-β(转化生长因子-β)家族成员是一类结构和功能相关的细胞因子，在胚胎发育过程中对细胞命运的调节和成人组织内环境的维持具有不同的作用。转化生长因子β家族信号的失调可导致一系列发育障碍和疾病，包括癌症、免疫功能障碍和纤维化。在这篇综述中，我们重点介绍转化生长因子β，一个特征明确的家族成员，在癌症进展过程中具有双重作用，在早期作为肿瘤抑制因子，在晚期作为肿瘤促进剂。转化生长因子β的功能不仅限于对癌细胞的增殖、分化、凋亡、上皮-间充质转化和转移的调节。最近的报道表明，转化生长因子β通过刺激细胞外基质沉积、促进血管生成和抑制抗肿瘤免疫反应而对肿瘤微环境中的细胞产生影响。转化生长因子β的促肿瘤作用引起了人们的广泛关注，因为它们的干预为癌症患者提供了一种治疗方法。然而，转化生长因子β在维持组织内稳态方面的关键作用使得靶向转化生长因子β成为一个挑战。在此，我们综述转化生长因子β在肿瘤发生发展中的多效性作用，总结转化生长因子β信号干预治疗癌症的最新临床进展，并讨论与靶向这一途径相关的剩余挑战和机遇。我们对将抗转化生长因子β治疗与细胞毒化疗、靶向治疗、放射治疗或免疫治疗相结合的协同治疗提供了展望。
Transforming growth factor-β (TGFβ) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development and in the maintenance of adult tissue homeostasis. Dysregulation of TGFβ family signaling can lead to a plethora of developmental disorders and diseases, including cancer, immune dysfunction, and fibrosis. In this review, we focus on TGFβ, a well-characterized family member that has a dichotomous role in cancer progression, acting in early stages as a tumor suppressor and in late stages as a tumor promoter. The functions of TGFβ are not limited to the regulation of proliferation, differentiation, apoptosis, epithelial–mesenchymal transition, and metastasis of cancer cells. Recent reports have related TGFβ to effects on cells that are present in the tumor microenvironment through the stimulation of extracellular matrix deposition, promotion of angiogenesis, and suppression of the anti-tumor immune reaction. The pro-oncogenic roles of TGFβ have attracted considerable attention because their intervention provides a therapeutic approach for cancer patients. However, the critical function of TGFβ in maintaining tissue homeostasis makes targeting TGFβ a challenge. Here, we review the pleiotropic functions of TGFβ in cancer initiation and progression, summarize the recent clinical advancements regarding TGFβ signaling interventions for cancer treatment, and discuss the remaining challenges and opportunities related to targeting this pathway. We provide a perspective on synergistic therapies that combine anti-TGFβ therapy with cytotoxic chemotherapy, targeted therapy, radiotherapy, or immunotherapy.
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影响因子：
11.2
作者：
Ardiani A;Gameiro SR;Palena C;Hamilton DH;Kwilas A;King TH;Schlom J;Hodge JW
通讯作者：
Hodge JW
影响因子：
64.8
作者：
AKHURST, RJ;FEE, F;BALMAIN, A
通讯作者：
BALMAIN, A
影响因子：
11.2
作者：
Bierie, Brian;Stover, Daniel G.;Moses, Harold L.
通讯作者：
Moses, Harold L.
影响因子：
64.5
作者：
BATTEGAY, EJ;RAINES, EW;ROSS, R
通讯作者：
ROSS, R
DOI：
10.1634/theoncologist.2009-s101
发表时间：
2010
期刊：
The oncologist
影响因子：
--
作者：
Anscher MS
通讯作者：
Anscher MS