PROJECT SUMMARY/ABSTRACT - MOLECULAR MECHANISMS OF CANCER (MMC) The overarching goal of the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) Molecular Mechanisms of Cancer (MMC) Program is to catalyze collaborative efforts that leverage emerging scientific discoveries from the laboratories of MMC scientists and propel them in a translational direction that makes an impact on cancer prevention, diagnosis, and treatment for patients living in our catchment area and beyond. The University of Chicago is a hotbed of scientific innovation, and the MMC continues to maximize the health benefits that emerge from this science, informed by the people most affected by cancer in our community. The MMC Program is centered on three key scientific and cancer- focused research themes: (1) deregulated gene expression and epigenetic defects in cancer; (2) altered cell growth and transformation; and (3) the tumor microenvironment in tumor growth and metastasis. These intersecting themes encompass the research of all members, across organ sites. The breadth and multi- disciplinary nature of our research contributes to the success of MMC in establishing productive translational collaborations both within MMC and across the other UCCCC programs. The MMC Program consists of 51 faculty members from 13 Departments, including 14 talented new faculty recruited to the institution in this funding cycle. In addition to increasing membership by 38% in this cycle, we increased the number and percentage of high-impact publications from 20% to 38% of total publications, increased NCI funding from $3.5M to $5M and launched 6 new working groups and multiple team science initiatives. Importantly, we have had increased success in moving our cutting-edge science into clinical trials, clinical applications, and/or commercialization. MMC leadership has fostered these successes by enhancing inter- programmatic collaborations, particularly with the UCCCC Clinical & Experimental Therapeutics Program via new working groups and targeted funding. Our work has a bidirectional relationship with the residents of our catchment area, who are negatively impacted by disparities in cancer incidence and mortality rates. Our work is informed by the community through multiple channels. In turn, our faculty and trainees are engaged in numerous educational and outreach opportunities to support our community. In this cycle, MMC will advance diversity, equity, and inclusion efforts by continuing to build an inclusive environment, increasing racial and gender diversity, and developing and retaining underrepresented minorities and women. Fostering the next generation of cancer researchers through extensive and interwoven education and training is a recognized hallmark of the MMC program that ensures our mission to reduce cancer burden and disparities.