We investigate how cancer cells sense, respond to stress, and ‘decide’ between transient or terminal fates. Our ultimate goal is to leverage this information to devise treatment strategies that selectively force cancer cells into terminal cell fates. We develop reporters of key players in the chemotherapy response and use live single-cell microscopy to measure the dynamics of these proteins after treatment. We found a link between heterogeneous activation of p53 and fractional killing of colon cancer cells after chemotherapy. We leveraged this information to design combination therapies that increase the fraction of apoptotic cells. We are continuing our work on p53 while also investigating the dynamics of the FOXO pathway.