TGFβ Signaling in the Pancreatic Tumor Microenvironment.
TGFβ Signaling in the Pancreatic Tumor Microenvironment.
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DOI：
10.3390/cancers13205086
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发表时间：
2021-10-11
期刊：
影响因子：
5.2
通讯作者：
Rana A
中科院分区：
文献类型：
--
作者：
Principe DR;Timbers KE;Atia LG;Koch RM;Rana A
对于晚期胰腺导管腺癌（PDAC）患者，目前尚无有效的治疗方法。转化生长因子β（TGFβ）信号转导与PDAC病理生物学的几个标志性特征有关，TGFβ抑制剂开始显示出治疗PDAC的前景。在这里，我们讨论了TGFβ信号传导在胰腺肿瘤微环境中的已知作用，以及在PDAC患者中评估TGFβ通路抑制剂的临床试验。胰腺导管腺癌（PDAC）与不良临床结局相关，主要归因于对标准治疗方法的不完全反应。最近，转化生长因子β（TGFβ）信号通路的选择性抑制剂已显示出在PDAC治疗中的早期前景，特别是作为增强对化疗和免疫治疗反应的手段。然而，TGFβ是一种有效的多效性细胞因子，在胰腺肿瘤微环境（TME）中具有几种看似矛盾的作用。尽管TGFβ信号传导可在上皮细胞中具有有效的肿瘤抑制作用，但TGFβ信号传导还通过增强上皮向间充质转化（EMT）、纤维化和逃避细胞毒性免疫监视程序来加速胰腺肿瘤发生。在这里，我们讨论了已知的TGFβ信号转导在胰腺癌发生中的作用，TGFβ通路的选择组分的遗传失活的生物学后果，以及过去和现在试图在PDAC患者的治疗中推进TGFβ抑制剂。
There is currently no effective treatment for patients with advanced pancreatic ductal adenocarcinoma (PDAC). Transforming Growth Factor β (TGFβ) signaling has been implicated in several hallmark features of PDAC pathobiology, and TGFβ inhibitors are beginning to show promise in the treatment of PDAC. Here, we discuss the known roles of TGFβ signaling in the pancreatic tumor microenvironment, as well as clinical trials evaluating TGFβ pathway inhibitors in PDAC patients. Pancreatic ductal adenocarcinoma (PDAC) is associated with poor clinical outcomes, largely attributed to incomplete responses to standard therapeutic approaches. Recently, selective inhibitors of the Transforming Growth Factor β (TGFβ) signaling pathway have shown early promise in the treatment of PDAC, particularly as a means of augmenting responses to chemo- and immunotherapies. However, TGFβ is a potent and pleiotropic cytokine with several seemingly paradoxical roles within the pancreatic tumor microenvironment (TME). Although TGFβ signaling can have potent tumor-suppressive effects in epithelial cells, TGFβ signaling also accelerates pancreatic tumorigenesis by enhancing epithelial-to-mesenchymal transition (EMT), fibrosis, and the evasion of the cytotoxic immune surveillance program. Here, we discuss the known roles of TGFβ signaling in pancreatic carcinogenesis, the biologic consequences of the genetic inactivation of select components of the TGFβ pathway, as well as past and present attempts to advance TGFβ inhibitors in the treatment of PDAC patients.
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