Lifestyle choices have long been known to have a major role in the development or prevention of cancer. Diet, chronic stress, smoking, poverty, physical activity, and socioeconomic variables are recognized as significant factors in prevention of cancer. Increasingly, these behaviors are studied as variables that affect cancer survivorship and response to treatment as well. One general mechanism through which diet could affect cancer growth is through promoting or inhibiting the accumulation of advanced glycation endproducts. Advanced glycation endproducts (AGEs) are reactive metabolites produced as by-products of sugar metabolism and oxidative stress. Furthermore, among PCa patients, AGE accumulation is higher in blacks with African ancestry (AAs) than in European Americans (EAs). As AGEs appear to promote cancer survival and growth, interventions to limit their accumulation may be viewed as potential cancer therapeutic agents. Chitosan, a polysaccharide obtained from shellfish or mushrooms that is thought to be poorly absorbed, directly binds AGE-modified proteins in aqueous solutions. No studies to date have demonstrated that chitosan can reduce either serum or tissue levels of AGEs in humans with AGE-related diseases. The investigators are conducting a Phase 1, assay-guided trial of chitosan in patients with prostate cancer on ADT and propose that chitosan will act as an absorbent of pre-formed AGEs, preventing their absorption from the gut and thus reducing their levels in the body. This intervention produced an 80% reduction in the plasma level of carboxymethyl lysine (CML) AGE adducts and more remarkably there was also a reduction in tissue AGE levels as determined by skin autofluorescence. These data support the idea that chitosan could be an active AGE-reducing agent that is clinically tolerable. Plasma and stool bio-fluid specimens have been collected from the four patients enrolled in the clinical trial and will be assayed. As these mechanistic studies are ongoing, the result will document any systemic effects from the chitosan intervention on inflammation, bowel permeability and microbiome diversity.

Citation Format: Shanora G Brown, Brandon Sutton, Taiwo Biotidara, Dave Turner, Robert Wilson, Michael Lilly. Mechanistic insights into phase 1b/2 study of chitosan for pharmacologic manipulation of AGE (advanced glycation endproducts) levels in prostate cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D062.