Project Summary/Abstract: Cancer Biology Program (CBP) The overall goal of research in the Cancer Biology Program (CBP), previously the Molecular and Biochemical Etiology Program, is to understand mechanisms that underlie cancer initiation and progression that could lead to new biomarkers and interventional strategies to positively impact cancer diagnosis, prevention, and therapeutic strategies across cancers prevalent in the BCC catchment area. To clearly delineate our mission and themes, we strategically reorganized the program to focus on basic cancer mechanisms, with translational efforts pursued in collaboration with the Targets, Modulators, and Delivery (TMDP) and GI Cancer (GICP) programs. To this end, we retained 14 prior members and added 24 new investigators with a basic cancer biology focus. The major goals of the CBP are to define the molecular mechanisms that maintain genome stability and their alterations in cancer, dissect intracellular signaling mechanisms and tumor cell-microenvironment interactions, and elucidate and harness metabolic and other mechanisms that lead to host systemic organ dysfunction and contribute to cancer patient morbidity and mortality. The 38 CBP members come from eight departments across the University with multidisciplinary interests in DNA damage/repair processes, signaling mechanisms, metabolomics, redox biology, and cell- and animal-based cancer models. The research interests of program members are organized around three Themes. Theme 1. Genome Instability and Cancer. Members focus on studies of genome replication, DNA damage responses and repair, and identification of new genomic alterations that drive hereditary or sporadic cancer. Theme 2. Signaling Mechanisms in Cancer. Members focus on elucidating intra- and inter-cellular signaling mechanisms that drive tumorigenesis and metastasis. Theme 3. Metabolic Alterations and Systemic Dysfunction in Cancer. Members focus on cancer cell metabolism and redox biology, and the impact of tumor burden on organ systems, with a particular focus on cancer cachexia and fatigue. There is extensive cross-talk between Themes, and basic mechanisms and pathways elucidated under CBP provide a rich basis for inter-programmatic collaborations with TMDP and GICP towards further translation into potential target validation and inhibitor design and translational studies. The Co-Leaders leverage their complementary expertise to enhance inter- and intra-programmatic collaborations through the development and employment of new and existing shared resources, evaluation and funding of pilot projects supporting the CBP mission, involvement in faculty recruitment, and organization of regular programmatic meetings. These activities have led to a strong collaborative group as demonstrated by impactful inter- and intra-programmatic, cancer- focused publications and grants, and an increased focus on basic biology with the potential for clinical translation. Cancer-relevant peer-reviewed...