This application for a Specialized Program of Research Excellence in Pancreatic Cancer focuses on translational studies that address basic and clinical issues of importance to improving the outcome of patients with pancreatic cancer. Specifically, the research projects in this program seek to: 1) develop and test novel therapeutic strategies including chemotherapy, and chemoradiation therapy for patients with early and advanced pancreatic cancer;2) undertake basic research studies in conjunction with clinical trials that will provide insight at the molecular level into the reasons for success and failure of the different strategies. The first project investigates potential of novel inhibitors of CDKS to block tumor progression and nociceptive signaling (pain) in preclinical animal models and in a phase I clinical trial in patients that have failed other therapies. The second project investigate further the molecular nature of radioresistance in patients with borderline resectable disease and proposes a clinical trial with inhibitors of the cholesterol synthesis pathway (Zometa) as a therapeutic intervention. The third project investigates therapeutic strategies that may be effective in SMAD4 mutant and SMAD4 wildtype tumors and proposes a novel clinical trial with a combination of an HDAC inhibitor (Belinostat) and an inhibitor to surviving (YM155) in patients that have failed other therapies. The fourth project investigates the possibility that a hypoxic an desmoplastic environment in pancreatic cancer affects metabolic features of the tumor and stroma that result in high endogenous production of cytidine, which in turn causes drug resistance to fluropyrimidines. Two therapeutic strategies that inhibit hypoxia (digoxin) and pyrimidine biosynthesis (leflunomide) will be investigated in a clinical trial, and the possibility that cytidine and associated metabolites can serve as biomarkers of drug resistance will be investigated. Our tissue core proposes to continue its unique collection of metastatic tumor samples through our rapid autopsy program, in addition to capturing samples associated with surgical resections. All projects are supported by administrative and biostatistics cores.
This application for a Specialized Program of Research Excellence in Gastrointestinal (Pancreatic Cancer) will focus on translational studies that address basic and clinical issues of importance to improving the outcome of patients with pancreatic cancer.
|Nimmakayala, Rama Krishna; Batra, Surinder K; Ponnusamy, Moorthy P (2018) Unraveling the journey of cancer stem cells from origin to metastasis. Biochim Biophys Acta Rev Cancer 1871:50-63|
|Aithal, Abhijit; Rauth, Sanchita; Kshirsagar, Prakash et al. (2018) MUC16 as a novel target for cancer therapy. Expert Opin Ther Targets 22:675-686|
|Barkeer, Srikanth; Chugh, Seema; Batra, Surinder K et al. (2018) Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis. Neoplasia 20:813-825|
|Naramura, Mayumi; Natarajan, Amarnath (2018) Mouse Pancreatic Tumor Model Independent of Tumor Suppressor Gene Inactivation. Pancreas 47:e27-e29|
|Contreras, Jacob I; Robb, Caroline M; King, Hannah M et al. (2018) Chemical Genetic Screens Identify Kinase Inhibitor Combinations that Target Anti-Apoptotic Proteins for Cancer Therapy. ACS Chem Biol 13:1148-1152|
|Wang, Gang; Biswas, Anup K; Ma, Wanchao et al. (2018) Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle. Nat Med 24:770-781|
|Murthy, Divya; Attri, Kuldeep S; Singh, Pankaj K (2018) Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics. Front Physiol 9:335|
|Barkeer, Srikanth; Chugh, Seema; Karmakar, Saswati et al. (2018) Novel role of O-glycosyltransferases GALNT3 and B3GNT3 in the self-renewal of pancreatic cancer stem cells. BMC Cancer 18:1157|
|Rana, Sandeep; Sonawane, Yogesh A; Taylor, Margaret A et al. (2018) Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy. Bioorg Med Chem Lett 28:3736-3740|
|Roy, Sohini; Bag, Arup K; Dutta, Samikshan et al. (2018) Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions. Cancer Res 78:5600-5617|
Showing the most recent 10 out of 191 publications