In Vivo Genome-Wide Pooled RNAi Screens in Cancer Cells to Identify Determinants of Chemotherapy/Drug Response

Large-scale RNAi screens (i.e., genome-wide arrays and pools) can reveal the essential biological functions of previously uncharacterized genes. Due to the nature of the selection process involved in screens, RNAi screens are also very useful for identifying genes involved in drug responses. The information gained from these screens could be used to predict a cancer patient’s response to a specific drug (i.e., precision medicine) or identify anti-cancer drug resistance genes, which could be targeted to improve treatment outcomes. In this capacity, screens have been most often performed in vitro. However, there is limitation to performing these screens in vitro: genes which are required in only an in vivo setting (e.g., rely on the tumor microenvironment for function) will not be identified. As such, it can be desirable to perform RNAi screens in vivo. Here we outline the additional technical details that should be considered for performing genome-wide RNAi drug screens of cancer cells under in vivo conditions (i.e., tumor xenografts).