Organ-on-a-Chip and Microfluidic Platforms for Oncology in the UK

SIMPLE SUMMARY: Organ-on-a-chip models, or organ chips, are tiny devices designed to accurately recreate the natural physiology and mechanical forces that cells experience in the human body. Similar to computer microchips, though carrying fluid through channels instead of an electric current, organ-chips are lined with living human cells and their tiny channels can reproduce blood and/or airflow just as in the human body. Their flexibility allows the chips to recreate breathing motions or undergo muscle contractions. This new and rapidly expanding field of research provides a unique opportunity to build models of human organs and to study how cancer cells develop and spread within them. As these chips are simpler and cheaper than animal models of cancer, they could significantly increase the speed of drug discovery and testing in cancer research. This exciting potential has led to the rapid development of this technology in the United Kingdom, with active research on a range of cancer types. This review covers the broad sweep of organ-chip research in the UK, and the network of researchers and companies being developed. Finally, it concludes with a perspective on the future directions in the field as researchers aim to bring about a leap forward in cancer therapies. ABSTRACT: Organ-on-chip systems are capable of replicating complex tissue structures and physiological phenomena. The fine control of biochemical and biomechanical cues within these microphysiological systems provides opportunities for cancer researchers to build complex models of the tumour microenvironment. Interest in applying organ chips to investigate mechanisms such as metastatsis and to test therapeutics has grown rapidly, and this review draws together the published research using these microfluidic platforms to study cancer. We focus on both in-house systems and commercial platforms being used in the UK for fundamental discovery science and therapeutics testing. We cover the wide variety of cancers being investigated, ranging from common carcinomas to rare sarcomas, as well as secondary cancers. We also cover the broad sweep of different matrix microenvironments, physiological mechanical stimuli and immunological effects being replicated in these models. We examine microfluidic models specifically, rather than organoids or complex tissue or cell co-cultures, which have been reviewed elsewhere. However, there is increasing interest in incorporating organoids, spheroids and other tissue cultures into microfluidic organ chips and this overlap is included. Our review includes a commentary on cancer organ-chip models being developed and used in the UK, including work conducted by members of the UK Organ-on-a-Chip Technologies Network. We conclude with a reflection on the likely future of this rapidly expanding field of oncological research.