PROJECT SUMMARY: TUMOR BIOLOGY RESEARCH PROGRAM The Sylvester Comprehensive Cancer Center (Sylvester) Tumor Biology (TB) Research Program, led by Scott Welford, PhD, and Priyamvada Rai, PhD, is composed of 36 members in ten departments. The TB program fosters collaborative, primarily basic mechanistic cancer research, related to Sylvester’s high-priority cancers and the unmet needs of its four-county catchment area (CA). Over the current reporting period (6/1/2018- 5/31/23), Sylvester has provided significant support for TB program development, including funds for faculty recruitment, pilot grants, and acquisition of key resources to support transdisciplinary, translational, and team science. TB members have expertise in studying cancer cells and the tumor microenvironment (TME), including the signaling pathways that regulate biological stress responses, redox homeostasis, immune modulation, and inflammation. The program’s primary mission is to understand how tumors arise and progress and uncover mechanisms underlying chemotherapeutic resistance. To accomplish these goals, TB members have prioritized three scientific aims, to: 1) elucidate mechanisms underlying tumor initiation; 2) investigate the underpinnings of tumor progression and drug resistance; and 3) identify and characterize molecular vulnerabilities in cancer. The TB program holds a current research funding portfolio of $9.4M in direct peer-reviewed funding, including $5.1M from the NCI. Since the initial CCSG submission in 2018, program members have published 489 peer- reviewed, cancer-relevant papers: 23% were intra-programmatic and 30% were inter-programmatic (vs. 21% and 18%, respectively, in the 2018 submission), 32% were in journals with impact factors ≥10 (vs. 19% in the 2018 submission), and 67% involved collaborations with external institutions. TB members lead four training grants (three T32s, including renewal of the T32 Research Training Program in Surgical Oncology in 2021, and one R25). Expertise and services provided by all six Sylvester Shared Resources support TB members’ research. Recent achievements include the discovery of novel roles of both redox response mechanisms and protein adducts in activating oncogenic transcription networks, which led to a successful NCI P01 grant to study esophageal adenocarcinoma. Other notable achievements include the identification of AVPR1A, a G protein-coupled receptor target in castration-resistant prostate cancer, and obesity-induced signaling by the adipokine chemerin in renal cell cancer development. To advance translational and bench-to-bedside research, TB members collaborate with colleagues in the Translational and Clinical Oncology (TCO) Research Program to advance clinical trial development. Thus, TB is a basic science program that capitalizes on Sylvester’s infrastructure, resources, and environment to advance collaborative, innovative, and CA-relevant basic research in alignment with the Sylvester 2019-2023 Strategic Plan.