A review of microfluidic approaches for investigating cancer extravasation during metastasis

Abstract Metastases, or migration of cancers, are common and severe cancer complications. Although the 5-year survival rates of primary tumors have greatly improved, those of metastasis remain below 30%, highlighting the importance of investigating specific mechanisms and therapeutic approaches for metastasis. Microfluidic devices have emerged as a powerful platform for drug target identification and drug response screening and allow incorporation of complex interactions in the metastatic microenvironment as well as manipulation of individual factors. In this work, we review microfluidic devices that have been developed to study cancer cell migration and extravasation in response to mechanical (section ‘Microfluidic investigation of mechanical factors in cancer cell migration’), biochemical (section ‘Microfluidic investigation of biochemical signals in cancer cell invasion’), and cellular (section ‘Microfluidic metastasis-on-a-chip models for investigation of cancer extravasation’) signals. We highlight the device characteristics, discuss the discoveries enabled by these devices, and offer perspectives on future directions for microfluidic investigations of cancer metastasis, with the ultimate aim of identifying the essential factors for a ‘metastasis-on-a-chip’ platform to pursue more efficacious treatment approaches for cancer metastasis.