Cancer Health Disparities SPORE in Endometrial Cancer - Endometrial cancer (EC) is increasing in frequency and mortality and harbors one of the largest health disparities in US cancers. To address this disparity, we propose the Cancer Health Disparities SPORE in Endometrial Cancer that is comprised of a multi-disciplinary translational research team and a comprehensive approach to studying disparities in EC that incorporates both social and biological factors into the study design of each of our three Projects and makes use of three unique EC patient cohorts as well as novel pre-clinical mouse and organoid models. The overall mission of our SPORE is to define key biological factors (epigenetic aging in Project 1; microbiome and innate immunity in Project 2; metabolic reprogramming and allostatic load in Project 3) alongside measurable social factors that may drive more aggressive behavior or lead to worse EC outcomes (treatment response, survival). Our hypothesis is that disparities influencing social and biological factors are fundamental drivers of poorer outcomes for women with EC, including the inter-related biological factors of epigenetic age acceleration, microbial dysbiosis, a heightened innate immune system, metabolic reprogramming and increased allostatic load. To address this hypothesis, we will leverage the on-going Carolina Endometrial Cancer Study (CECS) as our first patient cohort, a NC state-wide population-based prospective study of >1,700 EC patients with survey and medical records data collection, acquisition of tumor samples, and ongoing follow-up to collect data on treatment response and survival. CECS integrates tumor biology with measurable clinical and social data as potential contributors to worse outcomes in EC patients, and this study is central to Projects 1 and 2. In addition, we will make use of a second patient cohort which is a prospective study of EC patients undergoing programmed cell death protein-1 (PD-1) inhibitor immunotherapy treatment (PROMOTE) and includes the collection of tumors, blood, rectal swabs and stool, which are to be analyzed in Project 2. Our third patient cohort consists of banked tumor/blood from EC patients at both UNC and MD Anderson for analysis in Project 3. To complement these patient cohorts, we plan more mechanistic studies in pre-clinical models, including a unique germ-free EC mouse model (Project 2) and EC organoids (Project 3). These three Projects are supported by four integrated Cores, including an Administrative Core, a Biospecimens/Pathology Core, a Biostatistics/Bioinformatics Core and a Community Outreach and Engagement Core as well as a Developmental Research Program and Career Enhancement Program for the next generation of ideas and investigators. By combining these three Projects into a single program that share both key resources (patient cohorts, four Cores) and critical clinical, social and biological measures, we will identify the most impactful factors for biomarker and therapeutic target development and immediate translation into clinical interventions to improve outcomes in EC patients.
