Translational research is a primary focus of IRCC and permeates the research projects of the other Divisions. It is now an unprecedented time with regard to emerging cancer diagnosis and therapy. Advances in genomic technologies have made it possible to sequence candidate oncogenes in cancers quickly and affordably, and a reasonably wide collection of tumors has been characterized by gene expression profiling, full exome and/or full genome sequencing. Soon the numbers will be in the thousands. These data provide critical information about the spectrum and frequencies of mutations in cancers and will facilitate the development of drugs against targets that are most frequently mutated. Despite the early successes of targeted therapies, it is also becoming evident that primary and acquired resistance will be major limitations. Most solid tumors will not yield to single-agent targeted therapies. Even in those cases in which a single agent dissolves the tumor, the victory is short lived and the tumors reemerge. More often, single-agent trials involving targeted therapies administered to solid tumors result in modest effects, or no responses, even when confined to patients who have mutations in the target oncogene. Clearly, there is much yet to understand about in vivo tumor biology and exploring resistance mechanisms is essential to decide what combination of drugs will treat resistant tumors or even to prevent the emergence of resistance. ECMO is a collective, multi-disciplinary endeavor based on the experience of a new generation of scientists trained to translate molecular information into better patient care. The aims of ECMO are to supplement traditional diagnostic and prognostic factors with tumor genomic signatures and with molecular characterization of therapeutic targets; the identification of deranged molecular pathways; the isolation and characterization of cancer stem cells; and the development of innovative preclinical platforms for high-fidelity anticipation of clinical findings in humans. This knowledge will be instrumental in fostering the concept and design of innovative, hypothesis-driven clinical trials in patients.