Generation of reactive oxygen species (ROS), a natural byproduct of oxygen metabolism, occurs in all aerobic organisms at a controlled rate. Cancer cells are subjected to numerous cellular insults, including dysregulated oncogenes and loss of their natural extracellular matrix (ECM) interactions that lead to the generation of high levels of ROS and selection for upregulation of anti-oxidant programs that allow adaptation to elevated ROS. Although cancer cells possess enhanced canonical antioxidant programs that neutralize ROS, they nevertheless exhibit prominent ROS levels in response to these insults, suggesting the existence of additional programs that allow cancer cells to tolerate elevated ROS.
My presentation will include a discussion of the evolving concepts about the role of oxidative stress and anti-oxidants in distinct processes associated with tumor initiation and progression and the potential for targeting anti-oxidants for therapeutic intervention. In addition, I will describe studies from our laboratory using 3-dimensional culture systems to model early events in breast cancer which have highlighted the critical role of oxidative stress in eliminating aberrantly proliferating breast epithelial cells, as well as the role of endogenous anti-oxidants in promoting proliferation and survival of pre-malignant cells. I will also discuss studies providing evidence for an unconventional mechanism whereby cancer cells co-opt the ROS-activated neuronal Ca2+-permeable TRPA1 channel in order to adapt to oxidative environments.