“Targeting Cellular Plasticity in Metastatic Breast Cancer”
Michael Wendt | University of Iowa
Differential induction and reversion of epithelial-mesenchymal transitions (EMT) create a high level of cellular heterogeneity in metastatic breast cancer. This cellular plasticity allows metastases to quickly adapt and evolve in response to therapeutic pressure. Recent findings by our group demonstrate several mechanisms by which metastatic breast cancers engage plasticity to interconvert between various metabolic and growth-factor driven programs as disseminated cells survive, adapt to, and colonize new organ systems. To model how specific tumor microenvironments influence cellular plasticity, we are utilizing in vivo and advanced 3D culture systems. These systems allow to evaluate combinations of metabolic and epigenetic modifiers together with targeted kinase inhibitors and immune based therapeutics. In this seminar we will explore some of the underlying mechanisms and inducers of EMT that drive tumor cell plasticity and heterogeneity in metastasis and how we are translating these findings to design innovative therapeutic protocols.
