The OHSU Knight Cancer Institute (Knight) is a matrix cancer center at the Oregon Health &Science University (OHSU) in Portland, Oregon. Founded in 1992 by Grover C. Bagby, Jr. M.D., the Knight has been broadly supported by the university administrative leaders, who have provided space and resources at steadily increasing levels. The Knight Cancer Institute has been supported by the NCI Cancer Center Support Grant since 1997. The OHSU Knight Cancer Institute has 151 members who belong to four scientific programs (Cancer Biology, Hematologic Malignancies, Solid Tumors, and Cancer Prevention and Control). Knight members utilize eight well-established shared resources to perform outstanding research, convert research findings into treatments and preventive agents, and design clinical trials to validate molecular targets. The new Director, Brian Druker, M.D. has sought to refocus the direction of the Knight onto the core values of changing cancer medicine. Institutional investments have added more than 200,000 sq ft in research and clinical space. Sixty-two new members have been added to the Knight, including significant changes in the senior leadership. A gift of $100 million from Phil and Penny Knight (to be given in installments over five to seven years) led to renaming the OHSU Cancer Institute to the OHSU Knight Cancer Institute. Our goal is to invest in people and programs that will advance our mission to make personalized cancer therapy and prevention a reality. As the recognized leader in personalized cancer therapies, our focus has been and will continue to be on investing to make personalized cancer therapy a reality. Investments in people and programs will help us achieve the following goals: 1.) Develop the methodology and capacity to rapidly and comprehensively interrogate individual patient tumors, 2.) Develop the capacity to organize the molecular data into interpretable, pathway focused information, 3.) Develop strategies to understand which pathway alterations are important, 4.) Develop a library of approved and investigational agents that are available to us for human use, 5.) Develop the capacity to rapidly test combinations of therapies targeting multiple genetic abnormalities in cancers, 6.) Develop novel clinical trial designs that will accommodate multi-agent therapies, 7.) Initiate innovative, multi-pathway phase I clinical trials to test our strategy.