Perspectives of TGF-β inhibition in pancreatic and hepatocellular carcinomas.
Perspectives of TGF-β inhibition in pancreatic and hepatocellular carcinomas.
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DOI：
10.18632/oncotarget.1569
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发表时间：
2014-01-15
期刊：
影响因子：
--
通讯作者：
Raymond E
中科院分区：
文献类型：
--
作者：
Neuzillet C;de Gramont A;Tijeras-Raballand A;de Mestier L;Cros J;Faivre S;Raymond E
晚期胰腺导管腺癌（PDAC）和肝细胞癌（HCC）是不可治愈的疾病，预后特别差。在过去的十年中，研究越来越关注癌细胞周围的微环境及其在肿瘤发生和进展中的作用。 PDAC 和 HCC 的病理特征显着不同：PDAC 通常是间质为主、促纤维增生、血管化不良的肿瘤，而 HCC 是细胞性且高度血管化的肿瘤。尽管存在这些非常不同的环境，PDAC 和 HCC 都将转化生长因子-β (TGF-β) 作为共同的关键信号传导介质，参与上皮间质转化、侵袭和间质肿瘤对话。最近，阻断 TGF-β 通路的新药已进入临床评估阶段，在晚期 PDAC 和 HCC 患者中显示出活性。 TGF-β信号传导很复杂，根据癌细胞的背景、空间和时间以及微环境介导促肿瘤和抗肿瘤活性。在这篇综述中，我们全面概述了 TGF-β 通路的作用及其在细胞和微环境水平上 PDAC 和 HCC 发生和进展中的失调。我们还总结了 TGF-β 作为 PDAC 和 HCC 治疗干预靶点作用的关键临床前和临床数据，并探索优化 TGF-β 抑制疗法的前景
Advanced pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are non-curable diseases with a particularly poor prognosis. Over the last decade, research has increasingly focused on the microenvironment surrounding cancer cells, and its role in tumour development and progression. PDAC and HCC differ markedly regarding their pathological features: PDAC are typically stromal-predominant, desmoplastic, poorly vascularized tumours, whereas HCC are cellular and highly vascularized. Despite these very different settings, PDAC and HCC share transforming growth factor-β (TGF-β) as a common key-signalling mediator, involved in epithelial-to-mesenchymal transition, invasion, and stroma-tumour dialogue. Recently, novel drugs blocking the TGF-β pathway have entered clinical evaluation demonstrating activity in patients with advanced PDAC and HCC. TGF-β signalling is complex and mediates both pro- and anti-tumoural activities in cancer cells depending on their context, in space and time, and their microenvironment. In this review we provide a comprehensive overview of the role of the TGF-β pathway and its deregulation in PDAC and HCC development and progression at the cellular and microenvironment levels. We also summarize key preclinical and clinical data on the role of TGF-β as a target for therapeutic intervention in PDAC and HCC, and explore perspectives to optimize TGF-β inhibition therapy
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DOI：
10.1158/1055-9965.epi-08-0630
发表时间：
2008-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Brune K;Hong SM;Li A;Yachida S;Abe T;Griffith M;Yang D;Omura N;Eshleman J;Canto M;Schulick R;Klein AP;Hruban RH;Iacobuzio-Donohue C;Goggins M
通讯作者：
Goggins M
影响因子：
29.4
作者：
Apte MV;Wilson JS;Lugea A;Pandol SJ
通讯作者：
Pandol SJ
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D
DOI：
10.1016/j.biocel.2009.03.001
发表时间：
2009-08-01
影响因子：
4
作者：
Atzori, Luigi;Poli, Giuseppe;Perra, Andrea
通讯作者：
Perra, Andrea