Department of Medical Oncology, DanaFarber Cancer Institute, Boston, Massachusetts 02215, USA.
Nat Rev Drug Discov. 2013 Mar;12(3):217-28. doi: 10.1038/nrd3870.
The role of stromal cells and the tumour microenvironment in general in modulating tumour sensitivity is increasingly becoming a key consideration for the development of active anticancer therapeutics. Here, we discuss how these tumour-stromal interactions affect tumour cell signalling, survival, proliferation and drug sensitivity. Particular emphasis is placed on the ability of stromal cells to confer - to tumour cells - resistance or sensitization to different classes of therapeutics, depending on the specific microenvironmental context. The mechanistic understanding of these microenvironmental interactions can influence the evaluation and selection of candidate agents for various cancers, in both the primary site as well as the metastatic setting. Progress in in vitro screening platforms as well as orthotopic and 'orthometastatic' xenograft mouse models has enabled comprehensive characterization of the impact of the tumour microenvironment on therapeutic efficacy. These recent advances can hopefully bridge the gap between preclinical studies and clinical trials of anticancer agents.
基质细胞和肿瘤微环境在调节肿瘤敏感性方面的作用，越来越成为开发有效的抗癌治疗方法的关键考虑因素。在这里，我们讨论这些肿瘤-基质相互作用如何影响肿瘤细胞的信号转导、存活、增殖和药物敏感性。特别强调的是，基质细胞根据特定的微环境背景，赋予肿瘤细胞对不同类别的治疗药物的耐药性或敏感性的能力。对这些微环境相互作用的机制理解，可以影响各种癌症候选药物的评估和选择，包括原发部位和转移部位。体外筛选平台以及原位和“同转移部位”异种移植小鼠模型的进展，使我们能够全面描述肿瘤微环境对治疗效果的影响。这些最新进展有望弥合抗癌药物的临床前研究和临床试验之间的差距。
