Regulated cell death and responses to starvation in cancer

Abstract Cells respond to stress by upregulating adaptive mechanisms that promote survival or by undergoing cell death when the stress is too severe. Cancer cells take advantage of stress responses in order to survive within harsh cancer microenvironments, and understanding which adaptive mechanisms are utilized to avoid cell death is critical to gaining new knowledge that may be exploited for cancer therapy. It has also become clear that there is not one, but in fact many different forms of cell death that can occur in response to stress, and our studies have contributed significantly in this area. We have shown that some mechanisms have unique effects on the dynamics of cell populations, and that some promote, while others may hinder, therapeutic responses. Our proposed research program will focus on two major areas of discovery: (1) How is cell death regulated in response to stress, and how do particular mechanisms contribute to controlling population dynamics? (2) How do cells respond to nutrient starvation through adaptive mechanisms that involve lysosomes? We will exploit recent findings and methods we have developed to study these overarching questions through an integrated set of cell biological approaches with a focus on imaging-based studies.