CLINICAL & TRANSLATIONAL ONCOLOGY PROGRAM: ABSTRACT The overarching goal of the Clinical & Translational Oncology Program (CTOP) is to bring together basic and clinical scientists to transform scientific discoveries into clinical applications in pursuit of the broader University of Arizona Cancer Center (UACC) mission to prevent, diagnose, and treat cancer in the Catchment Area and beyond. CTOP is a redesigned program that emerged from the long-standing Therapeutic Development Program. After rigorous review and addition of new imaging-focused members, the renamed Program expanded its focus from drug development to the full spectrum of translational and clinical research involving human subjects with cancer. CTOP is structured around three Specific Aims: (1) discover and optimize new agents, biomarkers, and imaging modalities for therapeutic translation; (2) develop mechanistic investigator- initiated trials (IITs) for translation or reverse translation; and (3) conduct clinical trials testing the efficacy of new or repurposed therapies. Critical advances in agent discovery and optimization in the past funding period include the FDA approval of afamelanotide for protection of skin from sun-induced UV mutagenesis, discovery of novel compounds for blocking autophagy and iron acquisition in tumors, discovery of numerous compounds that modulate oncogenic signaling, and identification of non-addictive lead compounds for the management of pain specifically from cancer or its treatment. CTOP Members have established a robust pipeline of IITs, including window-of-opportunity and integral biomarker designs, for mechanistic translation. During the current 5-year funding period, CTOP enrolled 2,534 patients to clinical trials including 1,167 to interventional treatment trials (233 IITs), representing a 6.8 fold increase compared to the prior period. High-impact IITs include those evaluating first-in-class NAE inhibitor pevonedistat in Acute Myeloid Leukemia (AML); repurposing bendamustine for preventing graft-vs-host disease in haplo-identical bone marrow transplant, of importance for UACC’s Catchment Area population; evaluating NVX-108 to enhance radiotherapy for glioblastoma multiforme; evaluating ficlatuzumab, an anti-HGF monoclonal antibody (mAb), in head and neck cancer; and evaluating dronabinol for opioid-dependent, bone-metastatic breast cancer. CTOP’s 52 Members have a peer-reviewed funding base of $4.9M (direct costs) of which $2.2M (45%) is from the National Cancer Institute, $2.6M (53%) from other National Institutes of Health sources, and $0.1M (2%) from other peer-reviewed sources, representing a 17% increase in peer-reviewed funding. CTOP Members were awarded 35 MPI grants totaling $23.5M in cancer-relevant direct costs. These MPIs included 14 R01s, two P01s, one U54s, and partnerships with 28 institutions across the country, of which four were NCI-designated cancer centers. Since 2016, Members authored 386 cancer-relevant publications, of whi...