Abstract 3409: AGEing and lifestyle after a cancer diagnosis: A balanced equilibrium for survivorship

Abstract

Abstract In the US, over 18 million people are living with a cancer diagnosis and that number may double by 2050. There is a need to unite research across the cancer continuum to address the needs of cancer survivors to ensure optimal quality of life and improve mortality outcomes. Health constructs that influence cancer survivorship are multifactorial, highly dynamic, and vary across the lifespan. This makes assigning their impact on the well-being and future outcomes of cancer survivors challenging. As a pathophysiological process that lies at the intersection between societal, environmental, and biological constructs, it is proposed that the irreversible accumulation of metabolites called advanced glycation end products (AGEs) can inform on quality of life and mortality outcomes for cancer survivors. It is proposed that AGE accumulation as a result of societal, environmental, and biological constructs overwhelm the fragile equilibrium that maintains AGE homoeostasis to impact tumor biology and cancer outcomes. The relationships between health constructs and AGE exposure are epitomized by nutritional behavior. The consumption of cheaper unhealthier often ultra-processed foods are inherently AGE laden and the excessive consumption of foods high in fats and sugars that promote obesity and increase cancer risk readily provide reactive intermediates that fuel AGE formation in cells and tissues. Our collaborative epidemiological studies assign high levels of AGE consumption with increased breast cancer risk, aggressiveness, and mortality, which is supported by translational studies showing that circulating AGE levels in breast cancer patients correlate with worse disease-free survival and other poor prognosis indicators. Critically, this group has also shown that chronic AGE consumption by mice increases prostate tumor growth (p<0.001), and causes a rapid progression through prostate intra-epithelial neoplasia (p=0.049), adenocarcinoma (p=0.042) and metastasis (p=0.001). Consumption of the high AGE diet caused a regulatory program of stromal activation conducive for tumor growth. As a bio-social determinant of health AGE accumulation and its pathogenic effects serve as informative and/or functional markers indicative of the current health status and well-being of cancer survivors and may inform of potential future outcomes. Our studies show that physical activity and dietary intervention (cardiac rehabilitation) reduced systemic AGE levels in breast cancer survivors. Therefore, prevention and control interventions aimed at reducing AGE exposure represent viable strategies for improving quality of life and disease recurrence for cancer survivors. This research was made possible in part by Grant Numbers R01-CA259415, R01-CA245143, R21-CA194469, and U54-CA210962 from NIH-NCI. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH. Citation Format: David P. Turner, Bradley A. Krisanits, Marvella E. Ford, Lindsay L. Peterson, Susan E. Steck, Paula D. Bos, Victoria J. Findlay. AGEing and lifestyle after a cancer diagnosis: A balanced equilibrium for survivorship [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3409.