SYSTEMS, PATHWAYS & TARGETS PROGRAM ABSTRACT/PROJECT SUMMARY The overarching goal of the Systems, Pathways & Targets (SPT) Program is to discover new critical mechanisms of cancer proliferation, survival and drug resistance that can be exploited for the development of novel treatments and diagnostics. SPT members include cell biologists, immunologists, geneticists, systems biologists, computational scientists, and clinicians who leverage diverse perspectives to build collaborative teams that tackle long-standing problems in cancer using bold and innovative approaches. SPT members work at different scales, from molecules and cells to tissues and organs, to study the fundamental biology of individual cancer cells and the interactions among cells in the tumor environment and metastatic sites. Several SPT members are physician-scientists with independent research programs and are well-positioned to translate discoveries from bench to bedside. Moreover, SPT leadership actively connects basic scientists with clinicians through Disease- Oriented Teams (DOTs) and the annual CFCCC Scientific Retreat. These interactions lead to new clinical trials and facilitate access to patient samples for research projects. A unique aspect of SPT is the integration of systems biology approaches to the study of cancer. This emerging emphasis has resulted in productive intra- and inter-programmatic collaborations and extramural funding including a NCI-U54 grant to support a Center in Cancer Systems Biology. SPT maximizes progress toward the identification of targets for cancer therapeutics and diagnostics by devoting resources to recruiting new faculty members, nurturing development of early career faculty, and supporting mid-career faculty members with cutting-edge research programs focused on cancer cell biology and therapeutic targeting. To promote collaboration, SPT supports working groups with shared interests and sponsors conferences and workshops. The Specific Aims of SPT are: to identify key targets in signaling networks, developmental pathways, and metabolic programs that are relevant to cancer initiation, progression, and therapeutic resistance; to support multidisciplinary teams that study how heterogeneity at the single cell level and cell-cell interactions can influence cancer progression and therapeutic resistance; and to enable clinical-basic science multidisciplinary research via DOTs to accelerate the translation of preclinical research. These efforts to discover critical pathways and survival mechanisms will reveal novel therapeutic targets for testing and validation in preclinical models, and eventually in clinical trials. Membership: 72 Members from 16 Departments and 5 Schools Funding: $3,467,881 NCI (Directs); $7,256,055 Other Peer-Reviewed (Directs) Accruals: Interventional: 133; Treatment: 130; Institutional/Investigator-Initiated: 98 Publications: Total: 793; High Impact Journal: 199 (25%); Intra-programmatic: 113 (14%); Inter-Programmatic: 106 ...