In this presentation we will discuss new methods for the computational assembly and experimental validation of gene regulatory network based approaches to study the activity of small-molecules in mouse and human cells. Specifically, we will address the interrogation of context specific models of regulation, inferred from primary data, to elucidate effector genes mediating compound mechanism of action in vitro and in vivo. The analysis can be specifically directed to the identification of biomarkers of drug activity, candidate targets to abrogate resistance, as well as candidate target for combination therapy. Furthermore, we will discuss various mechanisms supporting synergistic compound activity in cancer cells and discuss a systems biology approach that allows the identification of such synergistic combinations on a computational, predictive basis. Specific examples in high-grade glioma and non-small cancer adenocarcinoma will be discussed.

Citation Format: Andrea Califano. Interrogating gene regulatory networks to explore the boundary between chemistry and biology in cancer [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA10.