COLCATS

This project intends to use an innovative combination of genomic and post-genomic “high content” approaches for the discovery of relevant drug targets in colorectal cancer, and for the identification new chemical leads bypassing their antiapoptotic/pro-survival function. The main project novelties with respect to classical disease-based approaches reside in: (i) The use of live human xenografted tumor collections propagated in nude mice as starting material (A2, A3) as well as patient records-linked cryopreserved tumor banks (A3, A4), (ii) The cross validation of large scale transcriptome analysis performed on the starting material (A2, A3, A4) with high throughput/high content functional target validation in live cell assays running on automated flow cytometry and imaging platforms using siRNA banks (A1, A3), (iii) The construction by genetic engineering of artificial model tumor cell lines termed “Oncocells” stably overexpressing the selected target, and their use in automated high content screening assays for the identification of proapoptotic/antiproliferative leads from molecule collections (A1, A2), (iiii) The testing of lead compounds in target over-expressing colon cell lines and xenograft models in vitro (A4).