Establishment of a high-content screening platform in 3D in vitro models to screen and identify potential therapeutic targets for PDAC

Abstract

Three-dimensional (3D) in vitro models, emerged as a model between in vitro cell culture and in vivo tumor, mimicking tumor heterogeneity, exposure to oxygen and nutrients, representation of cancer stem cells (CSCs), and response for treatments that are concordant with in vivo tumors. In combination with high-throughput approaches, these models are opening new pathways for testing and development of therapies in a pre-clinical setting. In this plan of activity, a master's student will screen a bespoke library of about 1,500 small-molecule inhibitors including specific chemical and biological probes, chemogenomic libraries, and PROTACs in a platform of PDAC tumor spheroids, observing the modulation of phenotypes using an HCS platform and identifying potential targets for PDAC treatment. Spheroids will be evaluated regarding growth, cell death, autophagy, and cell cycle. Normal cells from human pancreas will be used as control and to determine selectivity. At the end of this project, we will identify new promising therapeutic targets for PDAC that will be further characterized with dose-response assays.