Pancreatic cancer is an extremely lethal cancer. On average, patients who are diagnosed with pancreatic cancer succumb to the disease within 6 months. Research is the only way to defeat pancreatic cancer. My lab is making progress toward finding a cure by detecting the disease earlier and designing novel therapeutic approaches.
David Tuveson’s lab uses mouse and human tissue models of neoplasia to explore the fundamental biology of these diseases and thereby identify new diagnostic and treatment strategies. His team’s main focus is pancreatic cancer, a lethal malignancy that has eluded clinical solutions despite intensive study. The lab’s approaches at CSHL run the gamut from designing new model systems of disease to inventing new therapeutic and diagnostic platforms for rapid evaluation in preclinical and clinical settings. For example, they have adopted a new method of culturing tissue fragments indefinitely in cell culture, enabling deep analysis with genetic and pharmacological probes. In addition, therapeutic experiments in mouse models have revealed an important role of redox metabolism and stromal interactions on influencing therapeutic response. This year, they used the mouse model system to identify the mechanism of a promising drug treatment for pancreatic cancer. The lab found that using the drug in combination with more standard chemotherapeutic drugs stopped the tumor growth and lengthened life span for the mice, suggesting that the combination therapy may help overcome the drug resistance that is so commonly found in cancers. Tuveson’s lab also has a strong link to clinical trials locally and internationally, with confirmation in early-phase trials the ultimate goal. Collectively, their strategy in the preclinical and clinical arena is codified as the “Cancer Therapeutics Initiative,” and this initiative will provide these same approaches to the entire CSHL cancer community.
Dr. Tuveson serves as Director of the Lustgarten Foundation Pancreatic Research Laboratory at CSHL and as Director of Research for the Lustgarten Foundation.
Jacobetz, M. A. and Chan, D. S. and Neesse, A. and Bapiro, T. E. and Cook, N. and Frese, K. K. and Feig, C. and Nakagawa, T. and Caldwell, M. E. and Zecchini, H. I. and Lolkema, M. P. and Jiang, P. and Kultti, A. and Thompson, C. B. and Maneval, D. C. and Jodrell, D. I. and Frost, G. I. and Shepard, H. M. and Skepper, J. N. and Tuveson, D. A. (2013) Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut, 62(1) pp. 112-20.
Perez-Mancera, P. A. and Rust, A. G. and van der Weyden, L. and Kristiansen, G. and Li, A. and Sarver, A. L. and Silverstein, K. A. and Grutzmann, R. and Aust, D. and Rummele, P. and Knosel, T. and Herd, C. and Stemple, D. L. and Kettleborough, R. and Brosnan, J. A. and Li, A. and Morgan, R. and Knight, S. and Yu, J. and Stegeman, S. and Collier, L. S. and ten Hoeve, J. J. and de Ridder, J. and Klein, A. P. and Goggins, M. and Hruban, R. H. and Chang, D. K. and Biankin, A. V. and Grimmond, S. M. and Wessels, L. F. and Wood, S. A. and Iacobuzio-Donahue, C. A. and Pilarsky, C. and Largaespada, D. A. and Adams, D. J. and Tuveson, D. A. (2012) The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature, 486(7402) pp. 266-70.
Cook, N. and Frese, K. K. and Bapiro, T. E. and Jacobetz, M. A. and Gopinathan, A. and Miller, J. L. and Rao, S. S. and Demuth, T. and Howat, W. J. and Jodrell, D. I. and Tuveson, D. A. (2012) Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma. J Exp Med, 209(3) pp. 437-44.
Frese, K. K. and Neesse, A. and Cook, N. and Bapiro, T. E. and Lolkema, M. P. and Jodrell, D. I. and Tuveson, D. A. (2012) nab-Paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov, 2(3) pp. 260-9.
DeNicola, G. M. and Karreth, F. A. and Humpton, T. J. and Gopinathan, A. and Wei, C. and Frese, K. and Mangal, D. and Yu, K. H. and Yeo, C. J. and Calhoun, E. S. and Scrimieri, F. and Winter, J. M. and Hruban, R. H. and Iacobuzio-Donahue, C. and Kern, S. E. and Blair, I. A. and Tuveson, D. A. (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature, 475(7354) pp. 106-9.Additional materials of the author at
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