Alternative vascularization mechanisms in cancer -: Pathology and therapeutic implications
Alternative vascularization mechanisms in cancer -: Pathology and therapeutic implications
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DOI：
10.2353/ajpath.2007.060302
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发表时间：
2007-01-01
影响因子：
6
通讯作者：
Timar, Jozsef
中科院分区：
文献类型：
--
作者：
Dome, Balazs;Hendrix, Mary J. C.;Timar, Jozsef
虽然癌细胞通常不受正常调节机制的控制，但肿瘤生长高度依赖于氧、营养物和宿主衍生调节剂的供应。现在已经确定，肿瘤血管系统不一定来源于内皮细胞发芽;相反，癌组织可以通过预先存在的血管的共选择、内陷性微血管生长、出生后血管发生、肾小球样血管发生或血管发生拟态来获得其血管系统。最著名的驱动肿瘤血管形成的分子途径是缺氧适应机制。然而，广泛多样的遗传畸变谱与“血管生成表型”的发展相关。基于这些知识，在过去的十年中开发了新形式的抗血管治疗方法。当应用这些靶向治疗时，肿瘤进展的阶段，给定癌症组织的血管化类型以及血管化过程背后的分子机制都需要考虑。另一个挑战是找到最合适的抗血管治疗和标准放疗和化疗的组合。这篇综述旨在将我们在这一领域的最新知识整合到一个合理的策略中，这可能是发展有效的临床模式的基础，使用抗血管治疗癌症。
Although cancer cells are not generally controlled by normal regulatory mechanisms, tumor growth is highly dependent on the supply of oxygen, nutrients, and host-derived regulators. It is now established that tumor vasculature is not necessarily derived from endothelial cell sprouting; instead, cancer tissue can acquire its vasculature by co-option of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis, or vasculogenic mimicry. The best-known molecular pathway driving tumor vascularization is the hypoxia-adaptation mechanism. However, a broad and diverse spectrum of genetic aberrations is associated with the development of the "angiogenic phenotype." Based on this knowledge, novel forms of antivascular modalities have been developed in the past decade. When applying these targeted therapies, the stage of tumor progression, the type of vascularization of the given cancer tissue, and the molecular machinery behind the vascularization process all need to be considered. A further challenge is finding the most appropriate combinations of antivascular therapies and standard radio- and chemotherapies. This review intends to integrate our recent knowledge in this field into a rational strategy that could be the basis for developing effective clinical modalities using antivascular therapy for cancer.