Princeton University Physical Sciences-Oncology Center (PU PS-OC) will focus on how to control the evolution of cancer resistance to chemotherapy. Drug resistance is the major barrier to successful cancer treatment, and understanding its development will facilitate the creation of new agents with improved efficacy. These investigators will use the basics of physics to evaluate stress response mechanisms in a variety of fundamental as well as clinically relevant studies. This work will also focus on the evolution of this resistance to understand its origin and dynamics. The investigators hypothesize that evolution in a small, stressed microenvironment will generate the rapid emergence of resistance. This center will utilize novel microfabrication techniques and single cell genomic analysis to evaluate such a micro-environment amid metabolic and mechanical stressors. Moreover, these investigators will determine if stress can alter the types of mutations accumulated by cells. They will also address how a mutation can spread from an individual cell to the entire tumor.