The pancreas cancer microenvironment.
The pancreas cancer microenvironment.
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DOI：
10.1158/1078-0432.ccr-11-3114
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Tuveson DA
中科院分区：
文献类型：
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作者：
Feig C;Gopinathan A;Neesse A;Chan DS;Cook N;Tuveson DA
胰腺导管腺癌（Pancreatic ductal adenocarcinoma，PDA）是一种常见的恶性肿瘤，每年在全世界造成25万例死亡。尽管广泛的努力，细胞毒性和靶向治疗仅提供了有限的疗效PDA患者的日期。导致系统治疗失败的一个因素可能是PDA特有的大量肿瘤间质内容物。PDA基质，恰当地称为肿瘤微环境（TME），占据肿瘤块的大部分，并且由细胞外基质组分和非肿瘤细胞（包括成纤维细胞、血管和免疫细胞）的动态分类组成。最近的研究表明，PDA基质支持肿瘤生长并促进转移，同时作为药物递送的物理屏障。因此，正在积极研究改变基质组成或功能的方法，例如通过Notch/Hedgehog途径抑制干扰脉管系统或通过透明质酸酶缓解血管压迫。在这里，我们将回顾我们目前对PDA肿瘤微环境的理解，并强调进一步探索可能有益于患者的机会。
Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy, resulting in over 250,000 deaths per year world-wide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for PDA patients to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment (TME), occupies the majority of the tumor mass and consists of a dynamic assortment of extracellular matrix components and non-neoplastic cells including fibroblastic, vascular and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis, and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients.