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Science 324 (5933): 1457-1461

Copyright © 2009 by the American Association for the Advancement of Science

Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

Kenneth P. Olive,1 Michael A. Jacobetz,1,* Christian J. Davidson,2,* Aarthi Gopinathan,1,2,* Dominick McIntyre,1 Davina Honess,1 Basetti Madhu,1 Mae A. Goldgraben,1 Meredith E. Caldwell,1 David Allard,1 Kristopher K. Frese,1 Gina DeNicola,1,2 Christine Feig,1 Chelsea Combs,2 Stephen P. Winter,1 Heather Ireland-Zecchini,1 Stefanie Reichelt,1 William J. Howat,1 Alex Chang,3 Mousumi Dhara,3 Lifu Wang,2,4 Felix Rückert,5 Robert Grützmann,5 Christian Pilarsky,5 Kamel Izeradjene,6 Sunil R. Hingorani,6 Pearl Huang,7 Susan E. Davies,8 William Plunkett,9 Merrill Egorin,10 Ralph H. Hruban,3 Nigel Whitebread,11 Karen McGovern,11 Julian Adams,11 Christine Iacobuzio-Donahue,3 John Griffiths,1 David A. Tuveson1,{dagger}

Abstract: Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.

1 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK.
2 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Departments of Oncology and Pathology, The Sol Goldman Pancreatic Cancer Research Center, Sidney Cancer Center and Johns Hopkins University, Baltimore, MD 21287, USA.
4 Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
5 Department of Surgery, University Hospital Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
6 Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center (FHCRC), and University of Washington, Seattle, WA 98109, USA.
7 Oncology Franchise, Merck and Company, North Wales, PA 19454, USA.
8 Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge CB2 2QQ, UK.
9 M. D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
10 Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
11 Infinity Pharmaceuticals, Cambridge, MA 01239, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: david.tuveson{at}cancer.org.uk

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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C.-L. Lee, E. J. Moding, X. Huang, Y. Li, L. Z. Woodlief, R. C. Rodrigues, Y. Ma, and D. G. Kirsch (2012)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Cell Biol. 196, 395-406
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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S. Vong and R. Kalluri (2011)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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D. Z. Ewton, J. Hu, M. Vilenchik, X. Deng, K.-c. Luk, A. Polonskaia, A. F. Hoffman, K. Zipf, J. F. Boylan, and E. A. Friedman (2011)
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   Abstract »    Full Text »    PDF »
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S. B. Krantz, M. A. Shields, S. Dangi-Garimella, E. C. Cheon, M. R. Barron, R. F. Hwang, M. S. Rao, P. J. Grippo, D. J. Bentrem, and H. G. Munshi (2011)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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P. Timpson, E. J. McGhee, and K. I. Anderson (2011)
J. Cell Sci. 124, 2877-2890
   Abstract »    Full Text »    PDF »
Hedgehog Signaling: Networking to Nurture a Promalignant Tumor Microenvironment.
L. G. Harris, R. S. Samant, and L. A. Shevde (2011)
Mol. Cancer Res. 9, 1165-1174
   Abstract »    Full Text »    PDF »
Anti-VEGF Treatment-Resistant Pancreatic Cancers Secrete Proinflammatory Factors That Contribute to Malignant Progression by Inducing an EMT Cell Phenotype.
C. Carbone, T. Moccia, C. Zhu, G. Paradiso, A. Budillon, P. J. Chiao, J. L. Abbruzzese, and D. Melisi (2011)
Clin. Cancer Res. 17, 5822-5832
   Abstract »    Full Text »    PDF »
Tumor Engraftment in Nude Mice and Enrichment in Stroma- Related Gene Pathways Predict Poor Survival and Resistance to Gemcitabine in Patients with Pancreatic Cancer.
I. Garrido-Laguna, M. Uson, N. V. Rajeshkumar, A. C. Tan, E. de Oliveira, C. Karikari, M. C. Villaroel, A. Salomon, G. Taylor, R. Sharma, et al. (2011)
Clin. Cancer Res. 17, 5793-5800
   Abstract »    Full Text »    PDF »
Opportunities and Challenges in the Development of Experimental Drug Combinations for Cancer.
R. W. Humphrey, L. M. Brockway-Lunardi, D. T. Bonk, K. M. Dohoney, J. H. Doroshow, S. J. Meech, M. J. Ratain, S. L. Topalian, and D. M. Pardoll (2011)
J Natl Cancer Inst 103, 1222-1226
   Abstract »    Full Text »    PDF »
Micro-ultrasound for preclinical imaging.
F. S. Foster, J. Hossack, and S. L. Adamson (2011)
Interface Focus 1, 576-601
   Abstract »    Full Text »    PDF »
Combining Betulinic Acid and Mithramycin A Effectively Suppresses Pancreatic Cancer by Inhibiting Proliferation, Invasion, and Angiogenesis.
Y. Gao, Z. Jia, X. Kong, Q. Li, D. Z. Chang, D. Wei, X. Le, H. Suyun, S. Huang, L. Wang, et al. (2011)
Cancer Res. 71, 5182-5193
   Abstract »    Full Text »    PDF »
PTEN Is a Major Tumor Suppressor in Pancreatic Ductal Adenocarcinoma and Regulates an NF-{kappa}B-Cytokine Network.
H. Ying, K. G. Elpek, A. Vinjamoori, S. M. Zimmerman, G. C. Chu, H. Yan, E. Fletcher-Sananikone, H. Zhang, Y. Liu, W. Wang, et al. (2011)
Cancer Discovery 1, 158-169
   Abstract »    Full Text »    PDF »
Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity.
S. Singh, Z. Wang, D. Liang Fei, K. E. Black, J. A. Goetz, R. Tokhunts, C. Giambelli, J. Rodriguez-Blanco, J. Long, E. Lee, et al. (2011)
Cancer Res. 71, 4454-4463
   Abstract »    Full Text »    PDF »
Foretinib (GSK1363089), an Orally Available Multikinase Inhibitor of c-Met and VEGFR-2, Blocks Proliferation, Induces Anoikis, and Impairs Ovarian Cancer Metastasis.
M. Zillhardt, S.-M. Park, I. L. Romero, K. Sawada, A. Montag, T. Krausz, S. D. Yamada, M. E. Peter, and E. Lengyel (2011)
Clin. Cancer Res. 17, 4042-4051
   Abstract »    Full Text »    PDF »
In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging.
S. Eser, M. Messer, P. Eser, A. von Werder, B. Seidler, M. Bajbouj, R. Vogelmann, A. Meining, J. von Burstin, H. Algul, et al. (2011)
PNAS 108, 9945-9950
   Abstract »    Full Text »    PDF »
Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells.
W. Chen, T. Tang, J. Eastham-Anderson, D. Dunlap, B. Alicke, M. Nannini, S. Gould, R. Yauch, Z. Modrusan, K. J. DuPree, et al. (2011)
PNAS 108, 9589-9594
   Abstract »    Full Text »    PDF »

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