Integrated Cancer Biology Program at Duke is one of the NCI funded cancer systems biology programs and represents a collaboration that combines biological and analytic resources and expertise at Duke University, the Dana Farber Cancer Institute, Arizona State University, and the University of Southern California. The Duke ICBP (DICBP) is developing data and computational tools focused on an integrative and in-depth understanding of cell signaling pathways that are central to the control of cell proliferation and the oncogenic process. This core biological context - interconnected oncogenic signaling pathways including the Ras, Myc, Rb-E2F pathways, and the p53 response pathway - is fundamental to the control of cells moving from quiescence through G1 and into S phase, and link the activity of the cellular proliferation process with the determination of cell fate. Myriad aspect of deregulation of these pathways relate to the development of human cancer. The DICBP is developing genomic-scale measures of gene expression, sequence, metabolic and protein data whose analysis and interpretation will underlie the development of a comprehensive understanding of the complex regulatory networks that involves these pathways. The Program is a cohesive program involving a multi-disciplinary team of investigators, and integrates the development of biological investigation with the development and application of statistical models and computational tools for the analysis of such data.

Beyond these core goals of improving our understanding of the genomics and genetics of these pathways and the ability to understand complex patterns of pathway deregulation at a fundamental level, the DICBP aims to translate this information into clinical genomics, especially in studies in human breast cancer. Here we will make use of the detailed datasets and large-scale, complex information arising to refine and improve predictive models of breast cancer outcomes based on genome-scale molecular data. The DICBP targets the unique opportunity to bring together basic studies of oncogenic pathways with the study of human cancer in a way that will help to inform each process. The program is also generating models and methods that will define a paradigm for broader application to other aspects of cellular signaling and other disease contexts.

DICBP research overlays an integrated and multi-faceted training program that serves as a training ground for young investigators at the interfaces of biology, genomics, and the statistical and computational sciences. Students, fellows and junior faculty researchers are engaged in the integrated multi-disciplinary mix that spans from the basic biological and mathematical sciences to clinical research settings. DICBP is also generating methods and tools that will be available for all interested researchers, including statistical analysis methods for complex genomic data in integrated pathway studies, and a web-based information management system to provide the tools for data access, utilization, and visualization of higher-order pathway and network data. The web-based system also serves as a project management resource to link the activities of Center investigators as well as a mechanism for dissemination of data and computational tools to the scientific community.