Kidney Cancer Program Project Summary / Abstract The DF/HCC Kidney Cancer Program performs innovative basic research into the molecular basis of kidney tumors. Scientific efforts within the current funding period focused on identifying meaningful biomarkers for early detection and prognosis, underlying mechanisms of disease biology, novel therapeutic targets for the various kidney cancer populations, and improved preclinical models for preliminary validation of these findings. The Program has made notable advances in mechanism-based classification and treatment of kidney cancers, rewarded by marked improvements in patient outcomes and with the 2019 Nobel Prize in Medicine awarded to longstanding SPORE co-leader W.KaelinDFCI for his seminal discovery of the mechanism by which cells sense oxygen. The Program is well positioned for a leading role in addressing critical questions that will be points of increasing emphasis in kidney cancers in the near future. The Program’s 42 members (29 primary and 13 secondary) represent six DF/HCC institutions and 9 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $2.1 million in direct costs from the NCI and $1.7 million from other sponsors. During the current funding period, primary Program members published 612 cancer-relevant papers. Of these, 40% were inter-institutional, 21% were intra- programmatic, and 47% were inter-programmatic collaborations between two or more DF/HCC members. In order to achieve the Program mission, we propose the following Specific Aims over the next CCSG funding period: 1) Identify and validate novel targets in kidney cancer and establish preclinical models to test new agents; 2) Leverage Program infrastructure to facilitate drug development and to identify molecular and biological predictors of prognosis and response to therapy; and 3) Ensure that the Program serves Massachusetts (our CCSG catchment area) and the nation through the development of cancer prevention and early detection strategies, community education, and training of future leaders in the field. To execute these Aims, we will take full advantage of DF/HCC’s collaborative infrastructure, core facilities, clinical trial systems, and structured processes for community engagement and cancer research training.