Pharmacological Impact of 3-Dimensional Extracellular Matrix on Tumor Cells

DESCRIPTION (provided by applicant): There is a strong need in drug discovery for cellular assays that better predict human responses to drugs. A key technical hurdle has been the difficulty of incorporating 3-dimensional extracellular matrix into a powerful assay format that is compatible with the high throughput approaches used for early drug discovery. In this proposal we intend to develop the methods and validating datasets that will allow the commercialization of a microchannel array device. The device consists of an automatable array of microfluidic channels specifically designed for the culture of mammalian cells in three-dimensional format. This means that potential drug molecules that rely on 3-dimensional matrix can be found, and that artifacts based on 2D monolayer culture can be avoided. This device will be used to produce a small molecule screen in an improved pancreatic cancer cell model that recapitulates the in vivo microenvironment. Compounds that modulate tumor cell function in an extracellular matrix- dependent manner will be isolated and characterized. PUBLIC HEALTH RELEVANCE: Cellular assays that are more predictive are greatly needed in the pharmaceutical industry to improve the success rate in clinical trials, and in biomedical research in general to increase our understanding of disease mechanisms. In this proposal we plan to develop and commercialize a microchannel array device that will enable more physiologically relevant cellular assays in a high throughput, automated format.