Combined Targeted Treatment to Eliminate Tumorigenic Cancer Stem Cells in Human Pancreatic Cancer

Jemal, 2005, Cancer statistics, 2005, CA Cancer J Clin, 55, 10, 10.3322/canjclin.55.1.10 Matano, 2000, Gemcitabine combined with continuous infusion 5-fluorouracil in advanced and symptomatic pancreatic cancer: a clinical benefit-oriented phase II study, Br J Cancer, 82, 1772, 10.1054/bjoc.1999.1139 Rothenberg, 1996, A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer, Ann Oncol, 7, 347, 10.1093/oxfordjournals.annonc.a010600 Al-Hajj, 2003, Prospective identification of tumorigenic breast cancer cells, Proc Natl Acad Sci U S A, 100, 3983, 10.1073/pnas.0530291100 Hermann, 2007, Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer, Cell Stem Cell, 1, 313, 10.1016/j.stem.2007.06.002 Bar, 2007, Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma, Stem Cells, 25, 2524, 10.1634/stemcells.2007-0166 Hermann, 2007, Metastatic cancer stem cells: a new target for anti-cancer therapy?, Cell Cycle, 7, 188, 10.4161/cc.7.2.5326 Goodell, 1996, Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo, J Exp Med, 183, 1797, 10.1084/jem.183.4.1797 Jimeno, 2009, A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development, Mol Cancer Ther, 8, 310, 10.1158/1535-7163.MCT-08-0924 Feldmann, 2007, Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers, Cancer Res, 67, 2187, 10.1158/0008-5472.CAN-06-3281 Huber, 2007, Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis, Kidney Int, 71, 771, 10.1038/sj.ki.5002112 Aoki, 2001, A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt, Proc Natl Acad Sci U S A, 98, 136, 10.1073/pnas.98.1.136 Rubio-Viqueira, 2006, An in vivo platform for translational drug development in pancreatic cancer, Clin Cancer Res, 12, 4652, 10.1158/1078-0432.CCR-06-0113 Li, 2007, Identification of pancreatic cancer stem cells, Cancer Res, 67, 1030, 10.1158/0008-5472.CAN-06-2030 Thayer, 2003, Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis, Nature, 425, 851, 10.1038/nature02009 Morton, 2007, Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis, Proc Natl Acad Sci U S A, 104, 5103, 10.1073/pnas.0701158104 Inoki, 2005, Dysregulation of the TSC-mTOR pathway in human disease, Nat Genet, 37, 19, 10.1038/ng1494 Yilmaz, 2006, Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells, Nature, 441, 475, 10.1038/nature04703 Zhou, 2007, Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance, Proc Natl Acad Sci U S A, 104, 16158, 10.1073/pnas.0702596104 Guba, 2002, Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor, Nat Med, 8, 128, 10.1038/nm0202-128 Immervoll, 2008, Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas, BMC Cancer, 8, 48, 10.1186/1471-2407-8-48 Maeda, 2008, CD133 expression is correlated with lymph node metastasis and vascular endothelial growth factor-C expression in pancreatic cancer, Br J Cancer, 98, 1389, 10.1038/sj.bjc.6604307 von Hoff D. GDC-0449 in metastatic basal cell carcinoma. Presented at: Annual Meeting of the American Association for Cancer Research; April 12–16, 2008; San Diego, CA. Williams, 2003, Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions, Proc Natl Acad Sci U S A, 100, 4616, 10.1073/pnas.0732813100 Clarke, 2006, Cancer stem cells–perspectives on current status and future directions: AACR Workshop on Cancer Stem Cells, Cancer Res, 66, 9339, 10.1158/0008-5472.CAN-06-3126 Dalerba, 2007, Cancer stem cells: models and concepts, Annu Rev Med, 58, 267, 10.1146/annurev.med.58.062105.204854 Zucchi, 2007, The properties of a mammary gland cancer stem cell, Proc Natl Acad Sci U S A, 104, 10476, 10.1073/pnas.0703071104