Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation.

摘要: Despite significant investments in cancer research and drug discovery/development, the rate of new approval is ≤5% most cases metastatic remain incurable. Ninety-five percent drugs fail clinical development because a lack therapeutic efficacy and/or unacceptable toxicity. One major factors responsible for low success anticancer failure preclinical models to adequately recapitulate complexity heterogeneity human cancer. For throughput capacity reasons, high-throughput screening growth inhibition assays almost exclusively use two-dimensional (2D) monolayers tumor cell lines cultured on tissue culture-treated plastic/glass surfaces serum-containing medium. However, these 2D line cultures three-dimensional (3D) context cells solid tumors even though microenvironment has been shown have profound effect responses. Tumor spheroids best characterized widely used 3D models; however, spheroid sizes tend be nonuniform, making them unsuitable testing. To circumvent this challenge, we developed defined size microwell arrays using nonadhesive hydrogels that are applicable wide variety fabricate size-controlled microtumors. We demonstrate hydrogel array platform can applied successfully generate hundreds uniform microtumors within 3-6 days from many cervical breast, as well head neck squamous carcinoma (HNSCC) cells. Moreover, controlling microwells allows precise control over Finally, application technology probe activation epidermal factor receptor (EGFR) signaling HNSCC response EGF cetuximab treatments, respectively. believe ability large numbers morphology will provide more physiological vitro investigate how influences pathway efficacy.