Experimental Therapeutics


Comparatively small numbers of children with cancer limit the definitive data from which to decide what, if any, benefit a novel anticancer agent may have in children. Hence there is a need for pre-clinical models of childhood cancer to screen the potential activity of new agents in transgenic or xenograft animal and cell culture models.

In the current post-genomic era, we are flooded with molecular pathways and targets and potential small molecule inhibitors, so it is essential that we have screens and/or models to select the most promising. Yet on a more basic level, the molecular targets amenable to drug therapy have largely not been identified for pediatric cancers. The capacity to genetically engineer mouse models of cancer by either knocking-out or knocking-in selected genes of interest affords the opportunity to follow in-vivo tumor progression (and regression) and metastases. Modern advances in small animal imaging provide a powerful platform for in-vivo functional imaging. Application of RNAi-based genome wide screens for target validation offers another powerful approach to exploit for development of new therapeutics in childhood cancers. Unlike adult cancers which typically result from multiple complex genetic changes, childhood cancers have less complex genetic developmental origins, making the potential for discovery flowing from RNAi-based methods very real.

We propose to recruit up to 4 investigators with expertise in mouse models, genome-wide screening, RNAi, and functional imaging to create the nucleus of an experimental therapeutics program. The objective would be to exploit pre-clinical cancer models and define and validate “drug-able” targets in pediatric cancers, some of which will likely be of importance to the cancers common among adults as well.