Translational aspects in targeting the stromal tumour microenvironment: from bench to bedside.
Translational aspects in targeting the stromal tumour microenvironment: from bench to bedside.
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DOI：
10.1016/j.nhtm.2016.03.001
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Mirnezami AH
中科院分区：
文献类型：
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作者：
Bhome R;Al Saihati HA;Goh RW;Bullock MD;Primrose JN;Thomas GJ;Sayan AE;Mirnezami AH
实体瘤不仅包含恶性细胞，而且包含多种基质细胞和细胞外基质蛋白。这些成分通过一系列信号传导途径相互作用，形成一个可促进或抑制癌症进展的适应性网络。迄今为止，大多数抗肿瘤化疗剂主要寻求靶向癌细胞。因此，由于肿瘤扩张期间的选择压力，由于克隆进化，抗性发展。在肿瘤微环境中激活或抑制其他细胞类型的概念相对较新，并且具有靶向遗传稳定且不太可能产生耐药性的细胞的优势。这篇综述概述了基质肿瘤微环境中的关键参与者，并讨论了可能提供治疗益处的潜在靶向策略。肿瘤间质由细胞外基质中的间充质细胞、免疫细胞和血管细胞组成。基质细胞和细胞外基质蛋白代表可用于癌症治疗的遗传稳定的靶标。许多体外和动物研究支持基质定向治疗的概念。床边○已经开发或重新利用了几种治疗策略来靶向基质。抗血管生成剂贝伐单抗是十多年前获准用于癌症治疗的首批特异性基质靶向药物之一。最近，间质的免疫调节已成为一种非常成功的策略，检查点抑制剂等新药将彻底改变癌症治疗。政府○资助机构应继续承认基质在癌症进展中与癌细胞本身同时发挥的关键作用。毫无疑问，未来最成功的治疗方案将同时处理“种子”和“土壤”。
Solid tumours comprise, not only malignant cells but also a variety of stromal cells and extracellular matrix proteins. These components interact via an array of signalling pathways to create an adaptable network that may act to promote or suppress cancer progression. To date, the majority of anti-tumour chemotherapeutic agents have principally sought to target the cancer cell. Consequently, resistance develops because of clonal evolution, as a result of selection pressure during tumour expansion. The concept of activating or inhibiting other cell types within the tumour microenvironment is relatively novel and has the advantage of targeting cells which are genetically stable and less likely to develop resistance. This review outlines key players in the stromal tumour microenvironment and discusses potential targeting strategies that may offer therapeutic benefit. Benchside ○ The tumour stroma consists of mesenchymal, immune and vascular cells housed in an extracellular matrix. Stromal cells and extracellular matrix proteins represent genetically stable targets which can be exploited in cancer treatment. Numerous in vitro and animal studies support the concept of stromal-directed treatment. Bedside ○ Several therapeutic strategies have been developed or repurposed to target the stroma. The anti-angiogenic agent bevacizumab was one of the first specific stromal-targeting agents to be licensed for cancer treatment over a decade ago. More recently, immune modulation of the stroma has become a hugely successful strategy, with novel drugs such as checkpoint inhibitors set to revolutionise cancer treatment. Governments ○ Funding bodies should continue to acknowledge the pivotal role that the stroma plays in cancer progression, in parallel with cancer cell itself. Undoubtedly, the most successful treatment regimens of the future will address both the “seed” and the “soil”.