Dr. Subhash Chauhan: Development of New Therapeutic Approaches for Pancreatic Cancer Treatment

Development of New Therapeutic Approaches for Pancreatic Cancer Treatment
Subhash Chauhan
University of Tennessee Health Science Center
Pancreatic cancer (PanCa), is the fourth leading cause of cancer related deaths in the United States due to the lack of early diagnosis and poor response to available therapeutics. Thus, identification of newer therapeutic approaches that can aid current therapeutics is highly desirable. We have defined multidimensional roles of MUC13 mucin in the pathogenesis and therapeutics/imaging of PanCa. We have reported that MUC13 is highly expressed in human pancreatic tumors but not in normal pancreas and its expression progressively increases with disease stage and metastasis. MUC13 enhances tumorigenesis through modulation of multiple oncogenes (HER2, PAK1, ERK, metastasin/S100A4, TERT, sonic hedgehog (SHH), GATA-1) associated with tumorigenesis/metastasis and desmoplasia. We have also observed a functional interaction of MUC13 and HER2 in PanCa cells and identified miR-145 as a tumor suppressor and a novel regulator of MUC13 in PanCa. Additionally, we have identified drugs, ormeloxifene (ORM), curcumin (CUR) that inhibit tumor desmoplasia (targets SHH pathway) and enhances therapeutic response of gemcitabine, thus, can be of therapeutic benefit for PanCa. Moreover, we have generated unique anti-MUC13 mouse monoclonal (MAb) and recombinant humanized (HuAb) antibodies that can efficiently target pancreatic tumors. Furthermore, we have successfully generated multiple patented nanoparticle formulations for antibody guided tumor specific targeted drug delivery and imaging. Taken together, our data suggest a crucial role of MUC13 in PanCa pathogenesis. Thus, we hypothesize that “MUC13 proffers to the pathogenesis and metastasis of pancreatic cancer and can serve as a potential target for antibody guided nanotherapies and imaging”. Utilization of a novel anti-MUC13 monoclonal antibody can be used for the targeted tumor specific delivery of novel nanoparticle formulations in pancreatic tumors. This research will establish the multifaceted role of MUC13 in pathogenesis of PanCa and advance diagnosis and therapy of PanCa to reduce the morbidity and mortality caused by this devastating disease.
Primary research interest of Dr. Chauhan’s lab is to identify and characterize the diagnostic and therapeutic targets for cancer. Main focus of our research group is to elucidate the regulatory mechanisms of cell-cell adhesion and anti-adhesion molecules that cause cancers. This research is aimed for the identification and characterization of biomarkers that aberrantly express or localize in cancer cells in order to develop newer tools for early disease diagnosis. We are utilizing genomics and proteomics approach for identification of novel early diagnostic markers. Recently we have identified a novel trans-membrane mucin MUC13 which is highly over-expressed ovarian and pancreatic and colon cancer cells. This may be potential biomarker for early cancer diagnosis as well as a good target for antibody guided targeted cancer therapy. My laboratory is also conducting cancer health disparity research.

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