Ivey Jill W, Bonakdar Mohammad, Kanitkar Akanksha, Davalos Rafael V, Verbridge Scott S
Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA.
Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
Cancer Lett. 2016 Sep 28;380(1):330-9. doi: 10.1016/j.canlet.2015.12.019. Epub 2015 Dec 24.
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.
肿瘤在患者、组织、细胞和分子水平上具有高度异质性。这种多尺度异质性给有效治疗带来了重大挑战，理想的治疗方法不仅要区分肿瘤组织和健康组织，还要全面应对各种各样的肿瘤亚克隆。常用的治疗方法要么利用癌细胞的生物学表型（如高增殖率），要么不加区分地杀死目标体积内的所有细胞。肿瘤微环境（TME）靶向治疗是一个有前景的治疗方向，因为尽管存在潜在的基因异质性，但许多TME特征在不同肿瘤类型中是保守的。从历史上看，TME靶向治疗主要集中在支持肿瘤生长的细胞（如血管内皮细胞）上。然而，将TME中的内在物理和化学改变视为额外的治疗机会而非障碍，一类受TME启发的新型治疗方法有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成为改善癌症治疗的靶点。
