With the explosion of genomic data emerging from TCGA, COSMIC, and other cancer genome initiatives, there are fundamental challenges in:
• Discerning which mutant genes are critical cancer drivers
• Discerning oncogenes and tumor suppressors are connected in genetic / signaling networks.
Specifically, TNBC is often characterized by the co-incidence of multiple driver or driver and tumor suppressor mutations within a single tumor. Using genetically engineered cellular models that reflect clinically observed TNBC heterogeneity, we are employing forward genetics to characterize these genetic interactions and identify both the conserved and unique tumor stresses they confer. We will extend this line of research by systematically applying genetic, cell biologic, and biochemical approaches to understand the functions of these gene networks in controlling breast cancer pathogenesis and to predict how underlying genetic heterogeneity will impact response to targeted therapies.
