(156g) In Vitro Biomimetic Tumor Model with Cancer-Specific Gene Regulators and Green Fluorescence Reporter for High Throughput Drug Screening

Although much scientific effort has been expended for cancer treatment, this disease is still one of the leading causes of death around the world. The limitations and shortcomings of current therapies highlight the urgent need for more effective therapeutic strategies. So far, most of the chemotherapy drugs act negatively on the cell division without selection, leading to serious adverse effect on normal cells. The current mainstream of anti-cancer drug development is to find the drugs that have specific targets (DNA, mRNA or proteins). Those targets are overexpressed in cancerous cells and are critical for carcinogenesis. In this study, we engineered breast and lung cancer cells to express the enhanced green fluorescent protein (EGFP) under cancer-specific gene promoters for three known carcinogenesis genes - survivin, Bcl-2 and hTERT, which enable online high-throughput screening of drugs that may up- or down-regulate these cancer genes as indicative of efficacy in inhibiting breast and lung cancers. Additionally, the mechanism of drugs and the crosstalk between cancer genes can be elucidated at the early stage of drug discovery. Another issue in the pharmaceutical industry is the high drug failure rate owing to poor predictability of early drug assays in a two-dimensional cell culture system. In such traditional assay, multiple cell-cell and cell-matrix interactions are deficient, leading to incomprehensive cellar responses to drug agents. To improve the drug assay predictability, our assay has focused on the construction of three-dimensional biomimetic cancer cell models with the recapitulation of multiple elements of tumor microenvironment. While developing the new drug screening assay, we also combined the rapid cell detection approach to achieve the high-throughput capability. Our optimized drug screening process can help to discover more anti-cancer therapies.