LG235: Identification of mechanisms mediating response to therapy using integrative analysis of multi-omics tumor profiles

Friday, July 17, 2015 - 12:00
Vinay Varadan, MD
The etiology and progression of cancer involves coordinated deregulation of processes in the tumor and its microenvironment that are not yet fully understood. While genome-wide molecular profiling methods have enabled comprehensive measurement of changes at the RNA, DNA and epigenetic levels in tumors, analytic approaches to integrate these multi-omics profiles into biologically meaningful models have not yet matured. Furthermore, the number of genomic features measured per tumor sample far exceeds the number of samples in most cancer profiling studies, thus severely limiting the ability of standard statistical techniques to reliably discover associations in these datasets.  There is, therefore, a critical need for developing integrative computational frameworks that optimally leverage prior biological knowledge to infer mechanisms underlying cancer-related phenotypes. In this talk, I will outline our approach to identifying pathways and immune-related signatures that are predictive of response to therapy in breast cancer. I will also present a novel systems biology framework, InFlo, which enabled the identification of cAMP signaling as a key mediator of platinum resistance in ovarian cancer. These studies provide the motivation for the development of multi-scale integrative analytics that can delineate how interactions between the tumor and its microenvironment mediate response to therapy.