School of Biological and Health Systems Engineering (SBHSE), Arizona State University, Tempe, AZ, 85287, USA.
Department of Radiology, Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital, and Weill Cornell Medicine, New York, NY, 10021, USA.
Biomaterials. 2017 Jul;133:176-207. doi: 10.1016/j.biomaterials.2017.04.017. Epub 2017 Apr 21.
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.
根据世界卫生组织的数据，癌症是全球主要死因之一。尽管改善的治疗方法和早期诊断已经降低了与癌症相关的死亡率，但转移性疾病仍然是一个主要的临床挑战。局部肿瘤微环境在癌症转移中起着重要作用，肿瘤细胞对来自基质细胞和细胞外基质 (ECM) 蛋白的大量生化和生物物理信号做出反应并适应。由于这些复杂性，人们迫切需要了解癌症转移的分子机制，以促进更有效的治疗方法的发现。在过去的几年中，先进的生物材料和微工程方法的结合已经启动了用于癌症研究的创新平台技术的发展。这些技术使具有生理相关（即类似于体内）特征的仿生体外模型的创建成为可能，从而可以进行从基础癌症生物学到高通量药物筛选的各种研究。在这篇综述文章中，我们讨论了转移级联的每一步的生物学意义，并广泛概述了使用先进的生物材料和微工程技术再现这些阶段的最新进展。在每个部分中，我们将强调每种方法的优缺点，并对未来的方向提出我们的看法。
