TARGETING THE REGULATOR OF G PROTEIN SIGNALING 17 (RGS17) FOR LUNG AND PROSTATE CANCER TREATMENTS

Abstract

G‐Protein Coupled Receptors (GPCR) are one of the most important target in disease treatment with over 50% of all drugs on the market targeting these receptors. Regulator of G‐Protein Signaling (RGS) proteins are known to regulate the complex signaling pathways activated by GPCRs. Recent studies have implicated RGS‐proteins in the development and progression of pathologies, including some cancers. RGS17, the most‐recently identified family member of the RZ family of RGS proteins has been implicated in the growth, proliferation, metastasis and migration of prostate cancer cells as well as small‐cell and non‐small cell lung cancers. RGS17 is up‐regulated in lung and prostate tumors as much as 13 fold. RGS17 knockdown inhibits colony formation and decreases tumorigenesis in nude mice. Our studies implemented a high‐throughput screen campaign to determine the first Gαo: RGS17 protein: protein interaction (ppi) inhibitors. Immediate goals include determining the effectiveness of these compounds on inhibiting the GTPase acceleration activity of RGS17 in a steady‐state GTPase assay. The goal of this study is to establish lead compounds and develop a pharmacophore model for future avenues in cancer treatment. Research is supported by American Foundation for Pharmaceutical Education (AFPE), University of Iowa′s Center for Biocatalysis and Bioprocessing and The National Institutes of Health (R01CA160470).