My laboratory has shown that both tumor vasculature and normal vasculature under chronic inflammatory conditons or after radiation are dysfunctional due to nitric oxide synthases (NOS) uncoupling. Recoupling NOS with the BH4 metabolic precursor, sepiapterin, normalizes tumor vasculature resulting in increased tumor oxygenation and increased radiosensitivity and chemosensitivity. Oral sepiapterin also reduced radiation-induced heart and lung toxicities. Buffy coat DNA from the blood of patients in radiation oncology collected before, during, after therapy, and annually thereafter identified SNPs genes involved in endothelial function and fibrosis that are racially sensitive in terms of predicting radiotoxicities. Exosomes (and molecular constituents) isolated from the plasma samples are being used to determine their role in modifying the tumor microenvironment (e.g. immune suppression and as potential biomarkers of both treatment failure and late toxicities).
Angiogenesis,Animal models,Bioinformatics,Biomarkers,Cancer cell biology,Cancer diagnostics,Cancer disparities,Cancer therapy resistance,Cancer therapy toxicities,Cardiotoxicity,Cell signaling,Drug discovery,Genomics,Imaging,Immunotherapy,Inflammation,Metabolism,Obesity,Precision medicine,Radiotherapy,Signal transduction,Targeted therapies,Tumor microenvironment