02410nas a2200253   4500000000100000000000100001008004100002260001200043653002800055653001800083653001900101653001500120653001800135653002400153100003200177700002100209700002100230245005900251856005400310300001000364490000700374520176100381022001402142       2019                            d  c2019-0210aCancer microenvironment10aCancer models10aCancer therapy10ametastasis10amicrofluidics10aTumour angiogenesis1 aAlexandra Sontheimer-Phelps1 aBryan A. Hassell1 aDonald E. Ingber00aModelling cancer in microfluidic human organs-on-chips  uhttps://www.nature.com/articles/s41568-018-0104-6  a65-810 v193 aOne of the problems that has slowed the development and approval of new anticancer therapies is the lack of preclinical models that can be used to identify key molecular, cellular and biophysical features of human cancer progression. This is because most in vitro cancer models fail to faithfully recapitulate the local tissue and organ microenvironment in which tumours form, which substantially contributes to the complex pathophysiology of the disease. More complex in vitro cancer models have been developed, including transwell cell cultures, spheroids and organoids grown within flexible extracellular matrix gels, which better mimic normal and cancerous tissue development than cells maintained on conventional 2D substrates. But these models still lack the tissue–tissue interfaces, organ-level structures, fluid flows and mechanical cues that cells experience within living organs, and furthermore, it is difficult to collect samples from the different tissue microcompartments. In this Review, we outline how recent developments in microfluidic cell culture technology have led to the generation of human organs-on-chips (also known as organ chips) that are now being used to model cancer cell behaviour within human-relevant tissue and organ microenvironments in vitro. Organ chips enable experimentalists to vary local cellular, molecular, chemical and biophysical parameters in a controlled manner, both individually and in precise combinations, while analysing how they contribute to human cancer formation and progression and responses to therapy. We also discuss the challenges that must be overcome to ensure that organ chip models meet the needs of cancer researchers, drug developers and clinicians interested in personalized medicine.  a1474-1768