Targeted therapies and immunotherapies have transformed the clinical care of patients with metastatic cancer. By optimizing treatment with combinations of different therapies, a cure appears within reach for many cancers. However, achieving this goal will require more detailed knowledge of the mechanisms of therapy resistance and immune evasion and, importantly, of the impact of therapies on tumor evolution, which may promote or prevent subsequent therapy responses. The vision of my lab is to build and exploit this knowledge to identify rational combinations of existing and emerging therapies by understanding the complex and dynamic biology of cancer cells and the tumor microenvironment in all phases of therapy.