Advanced Glycation End Products Provide Insight into Tumor Associated Biosocial Synergy to Inform on Prostate Cancer Disparities

Prostate cancer (PCa) disparities present as a complex public health challenge rooted in a multifaceted interplay between biological, social, and environmental factors, herein termed biosocial synergy. Reactive metabolites known as Advanced Glycation End Products (AGEs) play a unique role at the nexus of biosocial synergy. Communities experiencing the highest cancer burden are more likely to be exposed to health inequity risk factors that increase AGE accumulation in the body, which has been linked to various chronic diseases. Previous research from our group demonstrated that nutritional inequity resulting from biosocial synergy enhances AGE bioavailability, influencing the tumor microenvironment and promoting PCa progression. Building on our published work, we are generating population specific patient-derived primary cell lines to investigate the mechanistic effects of AGE signaling on tumor biology, aiming to develop an innovative health inequity framework to address cancer disparity outcomes. Patients were consented according to our IRB protocol #20210623. Prostatectomy tissues were graded by our licensed pathologist and enzymatically processed into patient-matched epithelial and fibroblast population specific lines, which underwent molecular characterization. 2D and 3D co-culture models with these patient-matched lines were used to study the effects of AGEs on prostate tumor growth and the roles of AGE and receptor for AGE (RAGE) within the tumor microenvironment. To connect mechanism and epidemiology, we evaluated the correlation between AGE consumption and PCa outcomes using a diet questionnaire processed through an AGE algorithm. AGE introduction in the extracellular matrix replicated the activated response observed in prostate tumor tissues, evident in the differential ability of population specific fibroblasts to enhance epithelial cell migration via cancer-associated fibroblast (CAFs) activation. Direct AGE treatment also increased the invasive capacity of tumor epithelial cells cultured in 3D microfluidic co-cultures. This fostered a population specific pro-tumorigenic microenvironment conducive to tumor migration. In addition, epidemiological studies in a large patient cohort showed increased odds of aggressive PCa among Black men who consumed high levels of AGEs. There is a critical need for experimental models that can effectively reflect the highly dynamic nature of biosocial synergism on cancer outcomes. Increased AGE bioavailability offers an untapped opportunity to explore how biosocial synergy can impact tumor biology across population groups to promote aggressive disease. Reporting on transdisciplinary studies of AGE research could illuminate optimal strategies for overcoming health inequity barriers in cancer prevention, treatment, and survivorship for high-risk populations. Tuong Vi V. Nguyen, Boxiao Ding, Bradley A. Krisanits, Susan E. Steck, Steven C. Smith, Lance J. Hampton, Paula D. Bos, Nolan W. Wages, Victoria J. Findlay, David P. Turner. Advanced glycation end products provide insight into tumor associated biosocial synergy to inform on prostate cancer disparities [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A059.