Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment.
Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment.
复制标题
DOI：
10.1016/j.canlet.2015.12.019
复制
发表时间：
2016-09-28
期刊：
影响因子：
9.7
通讯作者：
Verbridge SS
中科院分区：
文献类型：
--
作者：
Ivey JW;Bonakdar M;Kanitkar A;Davalos RV;Verbridge SS
肿瘤在患者、组织、细胞和分子水平上是高度异质性的。这种多尺度异质性对有效疗法提出了重大挑战，理想情况下，有效疗法不仅必须区分肿瘤组织和健康组织，而且还必须完全解决各种各样的肿瘤亚克隆。通常使用的疗法利用癌细胞的生物表型（例如高增殖率）或不加区别地杀死靶体积中存在的所有细胞。肿瘤微环境（TME）靶向治疗代表了一个有前途的治疗方向，因为尽管存在潜在的遗传异质性，但许多TME标志在不同的肿瘤类型中是保守的。历史上，TME靶向主要集中在支持肿瘤生长的细胞（例如血管内皮细胞）上。然而，通过将TME内在的物理和化学变化视为额外的治疗机会而不是障碍，一类新的TME启发的治疗方法很有希望补充或取代现有的治疗策略。在这篇综述中，我们总结了TME的物理和化学特征，并讨论了这些肿瘤特征目前是如何，或最终可能是针对改善癌症治疗。
Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but also fully address the wide variety of tumorous sub-clones. Commonly used therapies either leverage a biological phenotype of cancer cells (e.g. high rate of proliferation) or indiscriminately kill all the cells present in a targeted volume. Tumor microenvironment (TME) targeting represents a promising therapeutic direction, because a number of TME hallmarks are conserved across different tumor types, despite the underlying genetic heterogeneity. Historically, TME targeting has largely focused on the cells that support tumor growth (e.g. vascular endothelial cells). However, by viewing the intrinsic physical and chemical alterations in the TME as additional therapeutic opportunities rather than barriers, a new class of TME-inspired treatments has great promise to complement or replace existing therapeutic strategies. In this review we summarize the physical and chemical hallmarks of the TME, and discuss how these tumor characteristics either currently are, or may ultimately be targeted to improve cancer therapies.