Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON, Canada.
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
SLAS Technol. 2019 Oct;24(5):457-476. doi: 10.1177/2472630319846878. Epub 2019 Jun 7.
A persistent challenge in developing personalized treatments for hematologic cancers is the lack of patient specific, physiologically relevant disease models to test investigational drugs in clinical trials and to select therapies in a clinical setting. Biomicrofluidic systems and organ-on-a-chip technologies have the potential to change how researchers approach the fundamental study of hematologic cancers and select clinical treatment for individual patient. Here, we review microfluidics cell-based technology with application toward studying hematologic tumor microenvironments (TMEs) for the purpose of drug discovery and clinical treatment selection. We provide an overview of state-of-the-art microfluidic systems designed to address questions related to hematologic TMEs and drug development. Given the need to develop personalized treatment platforms involving this technology, we review pharmaceutical drugs and different modes of immunotherapy for hematologic cancers, followed by key considerations for developing a physiologically relevant microfluidic companion diagnostic tool for mimicking different hematologic TMEs for testing with different drugs in clinical trials. Opportunities lie ahead for engineers to revolutionize conventional drug discovery strategies of hematologic cancers, including integrating cell-based microfluidics technology with machine learning and automation techniques, which may stimulate pharma and regulatory bodies to promote research and applications of microfluidics technology for drug development.
开发血液癌症个体化治疗的一个持续挑战是缺乏针对患者的、生理相关的疾病模型,以在临床试验中测试研究药物,并在临床环境中选择治疗方法。生物微流体系统和器官芯片技术有可能改变研究人员研究血液癌症的基本方法,并为个体患者选择临床治疗方法。在这里,我们回顾了基于细胞的微流控技术在血液肿瘤微环境(TME)研究中的应用,旨在进行药物发现和临床治疗选择。我们概述了用于解决与血液 TME 和药物开发相关问题的最先进的微流控系统。鉴于需要开发涉及该技术的个性化治疗平台,我们回顾了用于血液癌症的药物和不同免疫治疗模式,然后讨论了开发用于模拟不同血液 TME 的生理相关微流控伴随诊断工具的关键考虑因素,以便在临床试验中使用不同药物进行测试。工程师有机会彻底改变血液癌症的传统药物发现策略,包括将基于细胞的微流控技术与机器学习和自动化技术相结合,这可能会促使制药公司和监管机构推动微流控技术在药物开发方面的研究和应用。