PROJECT SUMMARY: Translational Oncology Research Program Jeffrey W. Tyner, Ph.D., and Lara Davis, M.D., Program Co-Leaders The goal of the Translational Oncology (TO) Program is to translate cutting-edge biology into high-impact interventions, with the aim of improving outcomes for patients with cancer. TO serves as the translational engine of the Knight Cancer Institute (KCI), collaborating with members of all KCI Programs to translate their findings into clinical investigations to benefit patients and advance understanding of the disease. TO research is organized into two themes 1) Target Validation and 2) High-Impact Interventions that align with and directly support the KCI Strategic Plan's foundations of Precision Early Detection and Precision Oncology. TO is a transdisciplinary program comprising 70 members from 18 departments, divisions, and institutes at OHSU. TO members produced 1,286 publications, of which 23% were intra-programmatic, 28% inter-programmatic and 70% inter-institutional collaborations. Total direct cost funding as of December 31, 2020 was $24,777,777, with peer-reviewed funding of $4,929,404 and $2,833,122 or 57% being from the NCI. TO activities, often in collaboration with other KCI Programs, have led to paradigm- and practice-changing impact across numerous catchment area priority cancers. These include the largest-to-date integrative multi-omic cancer dataset, which has been leveraged into cutting-edge clinical trials and is used by researchers around the world (Beat AML). Numerous practice-changing therapeutics, originating from collaborative, trans-programmatic discoveries, have been validated in pivotal trials in leukemia, sarcoma, and prostate cancer. The development of transformational platforms has enabled real-time allocation of novel combination therapies in a cancer-agnostic manner based on broad and deep tumor analytics conducted in a CLIA-approved environment. TO investigators also conducted clinical trials leading to the first-ever demonstration of drug class activity in specific cancer types (e.g., checkpoint blockade in prostate cancer). TO activities spearheaded precision early detection trials of non-invasive technologies with exquisite sensitivity that facilitate diagnosis, monitoring, and follow-up. These and other TO accomplishments engage the community and catchment area in a bidirectional manner where transformational research and novel therapies are made available to the community while patient and advocate engagement helps shape and inform research strategies. These activities also offer numerous opportunities for the education and training of the next generation of scientists and physician-researchers. The TO Program plans to build on the success of these existing projects with new endeavors, such as the Center for Experimental Therapeutics, which will provide a resource for drug development and rapid translation into clinical trials.