NEURO-ONCOLOGY (NRO) PROGRAM: PROJECT SUMMARY The Neuro-Oncology (NRO) Program seeks to understand the etiopathogenesis and progression of primary brain tumors and brain metastases and to use this knowledge to improve the overall survival and quality of life of patients. The three scientific focal areas within the Program include: (1) understanding the molecular underpinnings of brain tumor initiation and progression as well as cancer metastasis to the brain; (2) developing novel medical devices, techniques, and drug candidates to advance improved therapeutic approaches; and (3) designing innovative clinical trial interventions that will halt disease progression and limit the toxic effects of therapy. Although the NRO Program science broadly spans these three focal areas, the investigators have developed deep expertise in glioblastoma and breast and lung cancer brain metastases. As a reflection of this depth and a significant team science approach within the Program, NRO investigators secured a National Cancer Institute (NCI) P01 award focused on novel drug candidates and new ways of treatment delivery for glioblastoma, as well as nine new Department of Defense and NCI awards in breast cancer brain metastasis during the past few years. The NRO Program’s robust clinical trials portfolio also leverages a rich history of brain tumor research at the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) through long-standing participation in the NCI-funded Adult Brain Tumor Consortium and other national brain tumor collaborations. The portfolio also includes NRO investigator-initiated trials launched through WFBCCC’s NCI Community Oncology Research Program Research Base and other sponsored partnerships. Although WFBCCC has had a strong brain tumor/brain metastasis research focus for the past decade, the NRO Program was not formally organized until 2018 in response to recommendations by the WFBCCC External Advisory Board. The NRO Program now boasts 23 investigators and is co-led by two well-established scientists with distinct research expertise who have collaboratively built a highly synergistic Program – Waldemar Debinski, MD, PhD, an internationally-recognized translational scientist pioneering significant discoveries in identifying molecular targets for therapies, and Glenn Lesser, MD, a nationally recognized physician-scientist with an impressive track record in translating fundamental discoveries into clinical trials. The NRO Program’s total peer-reviewed, direct funding base is $4.9M, 75% from the NCI. Since 2016, this highly collaborative group of investigators authored a total of 157 neuro-oncology-focused research publications, of which 78 (50%) were intra-programmatic, 62 (39%) were inter- programmatic, and 81 (52%) were inter-institutional. Importantly, 20 (13%) of these publications involved seminal discoveries and translational breakthroughs published in top-tier journals such as the New England Journal of Medicine, Nature Neuroscience...