Novel Plasma Exosome Biomarkers for Prostate Cancer Progression in Co-Morbid Metabolic Disease
New diagnostic tools to assess risk of metastasis, chemoresistance and relapse in patients with prostate cancer are needed because cancer patient metabolism and metabolic medications are typically not considered clinically in evaluating these risks in prostate cancer. Investigators at Boston Medical Center led by medical oncologist Gretchen Gignac, MD, previously established that poorly controlled diabetes is strongly associated with progression to treatment resistance in men with prostate cancer [https://pubmed.ncbi.nlm.nih.gov/27515296]. The problem has broad implications, as the >50 million American men who are diabetic or pre-diabetic at present are insufficiently served the standard of care in prostate medical oncology, should they develop prostate cancer. Clinical decision making could be greatly improved for patients at-risk for cancer progression on account of their metabolic co-morbidities.
Increased body weight and obesity-driven (Type 2) diabetes have been established to be associated with increased circulating concentrations of “exosomes” and altered exosome content. Exosomes are extracellular vesicles of 50–200 nm in size that are released by most, or all, cells of the body. Importantly, they can contain bioactive molecules that are influenced by the metabolic status of the cell of origin. The ability of exosomes to circulate in blood and lymph suggest that these metabolic signals can travel throughout the body to deliver instructions to target tissues [https://pubmed.ncbi.nlm.nih.gov/35361917/].
Recent research results from Drs. Denis, Heaphy, Gignac and others, obtained in part though Shipley Center support [https://pubmed.ncbi.nlm.nih.gov/36644690/], show that human plasma contains exosomes with microRNAs (small, single-stranded, non-coding RNA molecules) capable of reprogramming prostate cancer cell properties, such as ‘epithelial-to-mesenchymal transition’, which associates with cancer aggressiveness and metastasis. The microRNA profiles of exosomes from adults with Type 2 diabetes are different from non-diabetic patients; Type 2 diabetes exosomes induce more dangerous changes in prostate cancer cells. Results show specific exosomal microRNAs that may be useful as potential blood biomarkers to assist clinical decision making in prostate cancer patients with Type 2 diabetes. The Type 2 diabetes exosomal microRNAs induce cancer aggressiveness gene sets in human prostate cancer models that are strongly correlated with human primary and metastatic prostate cancer samples obtained from human genetic datasets, confirming clinical importance of this new pathway.
These new findings suggest that plasma exosomes as noninvasive biomarkers might also assist endocrinologists to better manage treatment of patients with metabolic disease. In addition, drug delivery is a promising application of exosomes; for example, new approaches are being developed to engineer and develop exosomes for therapeutic targeting. Research is continuing with a wide range of prostate cancer patients to discover exosome expression patterns that associate with clinical and demographic variables and outcomes, to further develop this new biomarker.