CANCER THERAPEUTICS (CRX) – PROJECT SUMMARY/ABSTRACT Recent advances offer unprecedented opportunities to create new modes of diagnosing, imaging, and treating many types of cancer. The Cancer Therapeutics (CRX) Program exists to bring together University of Virginia Cancer Center (UVACC) investigators whose multi-disciplinary research programs collectively support preclinical science, validation of therapeutic targets, and translation of discoveries into investigator-initiated clinical trials (IITs). A hallmark of the CRX program is to drive discoveries and new technologies along the Translational Pipeline to obtain the UVACC's ultimate goal of reducing the burden of cancer in the catchment area and beyond. In addition to identifying immune therapeutic targets and developing immunotherapies (Aim 1), CRX advances other therapeutic and imaging discoveries, including those from the Cancer Biology (CBIO) and Molecular Genetics and Epigenetics (GEN) Programs through preclinical development (Aim 2) culminating in the initiation and performance of investigator-initiated clinical trials (IITs) of agents developed by UVA investigators (Aim 3). The CRX program is led by three co-leaders (Slingluff, Kelly, Landen) with complementary expertise in discovery science, translation, and clinical trials. The Program consists of 59 Members, 29 of whom are new to UVA or the UVACC since the prior renewal, from 16 departments and two schools. CRX Program Members lead the newly created Translational Research Teams, which facilitate the productive collaboration of members from all Programs to focus research efforts on four cancers identified to be particularly burdensome within the catchment area. CRX Members are principal investigators of grants totaling $5.54M of direct-cost peer-reviewed funding, $3.85M from NCI and $1.69M from other peer-reviewed sources. CRX depends on infrastructure created by the UVACC, especially the Molecular and Immunological Translational Sciences Core, Biorepository and Tissue Research Facility, Biostatistics Shared Resource, and the Office of Clinical Research. Together, these activities culminated in 407 selected publications since the last renewal. Of these, 25% have an impact factor of 10 or greater, 27% are intra-programmatic, 21% are inter- programmatic with other UVACC Programs, and 46% are collaborative with other NCI Cancer Centers.