Therapies that directly target cancer-promoting oncoproteins have revolutionized the treatment of cancer. Cancers, however, are primed to adapt and evolve in the presence of treatment, resulting in an ability to resume growth despite the presence of therapy. Utilizing cutting-edge new techniques that allow the determination of genetic alterations in single cancer cells, Piro aims to understand the principles that govern the evolution of resistance during therapy and identify novel therapeutic interventions that halt this process. His specific focus will be on improving the efficacy of KRAS inhibition for treatment of lung and colorectal cancers.