CANCER BIOLOGY PROGRAM: PROJECT SUMMARY The Virginia Commonwealth University (VCU) Massey Cancer Center (MCC) launched a new Cancer Biology (CB) Program in 2020, incorporating the strengths and expertise of select members from the former Cancer Cell Signaling and Cancer Molecular Genetics Programs. The objective of this restructuring was to build a more cohesive, cancer-centric, basic research program within MCC’s transdisciplinary environment that would enhance collaborative interactions and increase opportunities to seed new scientific concepts. These concepts could be further leveraged through team-based translation with members of the Developmental Therapeutics (DT) or Cancer Prevention and Control (CPC) Programs. CB Program members crafted an overarching scientific pillar goal through the 2021-2025 MCC Strategic Plan to guide their efforts forward – to achieve groundbreaking discoveries through unraveling mechanistic paradigms of tumorigenesis and dissecting key interactions between tumors and their stromal or immune microenvironment. The CB Program is organized under three specific aims focusing on cancer cell signaling, genetic and epigenetic drivers, and tumor microenvironment. CB Program members perform innovative research to understand the complex facets of cancer biology and in collaboration with DT and CPC members develop innovative preventative, diagnostic, and therapeutic tools to target specific cancers, especially those with the highest burden in MCC’s catchment area. Recently, the CB Program undertook initiatives to establish formal collaborations with the Office of Community Outreach and Engagement to ensure its members are fully aware of the distinct characteristics of the cancer burden in MCC’s catchment area so that they can best align their science to address this burden and engage the community in CB Program science going forward. With 47 members across six VCU Schools/Colleges, the CB Program has also cultivated a rich intellectual environment for attracting and mentoring an increasingly diverse pipeline of early-stage cancer biologists. CB Program members currently hold $7.8M in annual, direct, peer-reviewed funding ($3.1M from NCI; $3.3M from other NIH institutes; $1.4M from other agencies). Since 2016, members of the CB Program have published their discoveries in 433 program-relevant and cancer-focused research articles. Demonstrating the program’s collaborative nature, 141 (33%) publications were intra-programmatic, 132 (30%) were inter- programmatic, and 266 (61%) were inter-institutional. Among the many scientific contributions made by CB members since 2016, a few noteworthy include 1) defining the roles of two oncoproteins, AEG-1 and SND1, in hepatocellular carcinoma; 2) discovering a novel Activin/Twist1 axis in cancer cachexia that is amenable to therapeutic manipulation; 3) identifying PDZ1i as a potent anti-metastatic drug; 4) unraveling the ability of sphingosine kinase 1 to inhibit triple-negative breast cance...