The goal of the Developmental Research Program (DRP) of the NCI-supported Mayo Clinic SPORE in Hepatobiliary Cancers is to support innovative, scientifically sound research projects from which findings can be translated into clinically relevant interventions that reduce the burden of liver and biliary cancers, which are a leading cause of cancer related deaths that continues to grow. The success of this ongoing program in years 1- 4 of funding is evident from 11 new DRP projects, with 1 advancing to a full translational project in the renewal period. Building upon this successful track record, the DRP will continue to provide up to $50k per year ($25k from NCI SPORE funds plus $25k from matching institutional funds) to each of 2 projects per year, with the potential of a second year of support based on progress and promise. At least one of these awards will be to an investigator from an underrepresented racial/ethnic group. Potential high risk/high payoff innovative concepts are encouraged that utilize the extensive shared resources cores of the SPORE. A rigorous peer review process utilizing the expertise of the External Advisory Board and other experienced investigators, with additional input from the patient advocates and Community Engagement and Diversity Council, evaluates all applications based upon the following criteria: scientific merit, originality, qualifications of the applicant/co-investigator(s), and translational potential. Whereas the translational trajectory of all applications needs to be readily apparent, the priority is on potentially high payoff proposals investigating all aspects pertaining to the morbidity and mortality of hepatobiliary cancer from the bench to the population. This is accomplished through the following Specific Aims: 1) Solicit and support the most innovative and interdisciplinary translationally relevant laboratory, population science, and clinical studies in hepatobiliary cancer, 2) Encourage and seek out the recruitment of qualified minorities, women, and persons with disabilities, 3) Provide critical evaluation of all DRP applications and awardee progress, 4) Foster extensive scientific collaborations and facilitate the development of DRP funded proposals into independent extramural applications and/or future Hepatobiliary Cancer SPORE translational projects, and 5) Develop awardees as leaders of future SPORE projects, and as SPORE and Cancer Center leadership. Continued support from the SPORE is expected to lead to the generation of new hypotheses that will be tested in SPORE-sponsored research or other peer reviewed external grants. The long-term goal of the SPORE is to translate the findings generated by these developmental projects into a reduction in the incidence and mortality rates of liver and biliary cancers.