140
Views
11
CrossRef citations to date
0
Altmetric
Review

Challenges in developing targeted therapy for pancreatic adenocarcinoma

&
Pages 1389-1401 | Published online: 14 Oct 2008

Bibliography

  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58(2):71-96
  • Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363(9414):1049-57
  • Burris HA, III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15(6):2403-13
  • Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344(14):1031-7
  • Bramhall SR, Schulz J, Nemunaitis J, et al. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 2002;87(2):161-7
  • Van Cutsem E, Van De Velde H, Karasek P, et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004;22(8):1430-8
  • Bramhall SR, Rosemurgy A, Brown PD, et al. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 2001;19(15):3447-55
  • Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25(15):1960-6
  • Gatzemeier U. Targeting the HER1/EGFR receptor to improve outcomes in non-small-cell lung cancer. Oncology (Williston Park) 2003;17(11 Suppl 12):7-10
  • Rocha-Lima CM. New directions in the management of advanced pancreatic cancer: a review. Anticancer Drugs 2008;19(5):435-46
  • Hahn SA, Kern SE. Molecular genetics of exocrine pancreatic neoplasms. Surg Clin North Am 1995;75(5):857-69
  • Hansel DE, Kern SE, Hruban RH. Molecular pathogenesis of pancreatic cancer. Annu Rev Genomics Hum Genet 2003;4(1):237-56
  • Howe JR, Conlon KC. The molecular genetics of pancreatic cancer 54. Surg Oncol 1997;6(1):1-18
  • Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res 2000;6:2969
  • Hruban RH, Wilentz RE, Kern SE. Genetic progression in the pancreatic ducts. Am J Pathol 2000;156:1821
  • Lemoine NR. Molecular advances in pancreatic cancer. Digestion 1997;58(6):550-6
  • Sakorafas GH, Tsiotos GG. Molecular biology of pancreatic cancer: potential clinical implications. BioDrugs 2001;15(7):439-52
  • Lynch HT, Smyrk T, Kern SE, et al. Familial pancreatic cancer: a review. Semin Oncol 1996;23(2):251-75
  • Rieder H, Bartsch DK. Familial pancreatic cancer. Fam Cancer 2004;3(1):69-74
  • Sakorafas GH, Tsiotou AG, Tsiotos GG. Molecular biology of pancreatic cancer; oncogenes, tumour suppressor genes, growth factors, and their receptors from a clinical perspective. Cancer Treat Rev 2000;26(1):29-52
  • Freeman JW, DeArmond D, Lake M, et al. Alterations of cell signaling pathways in pancreatic cancer. Front Biosci 2004;9:1889-98
  • Basso AD, Kirschmeier P, Bishop WR. Lipid posttranslational modifications. Farnesyl transferase inhibitors. J Lipid Res 2006;47(1):15-31
  • Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 2007;26(22):3291-310
  • Shields JM, Pruitt K, McFall A, et al. Understanding Ras: ‘it ain't over ‘til it's over’. Trends Cell Biol 2000;10(4):147-54
  • Bancroft CC, Chen Z, Dong G, et al. Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-κB signal pathways. Clin Cancer Res 2001;7(2):435-42
  • Grunewald K, Lyons J, Frohlich A, et al. High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer 1989;43(6):1037-41
  • Smit VT, Boot AJ, Smits AM, et al. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 1988;16:7773
  • Calhoun ES, Jones JB, Ashfaq R, et al. BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol 2003;163(4):1255-60
  • Srivastava A, Alexander J, Lomakin I, Dayal Y. Immunohistochemical expression of transforming growth factor α and epidermal growth factor receptor in pancreatic endocrine tumors. Hum Pathol 2001;32(11):1184-9
  • Tobita K, Kijima H, Dowaki S, et al. Epidermal growth factor receptor expression in human pancreatic cancer: significance for liver metastasis. Int J Mol Med 2003;11(3):305-9
  • Gangarosa LM, Sizemore N, Graves-Deal R, et al. A raf-independent epidermal growth factor receptor autocrine loop is necessary for Ras transformation of rat intestinal epithelial cells. J Biol Chem 1997;272(30):18926-31
  • Minna JD, Gazdar AF, Sprang SR, Herz J. Cancer. A bull's eye for targeted lung cancer therapy. Science 2004;304(5676):1458-61
  • Gazdar AF, Shigematsu H, Herz J, Minna JD. Mutations and addiction to EGFR: the Achilles ‘heal’ of lung cancers? Trends mol med 2004;10(10):481-6
  • Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem 1990;265(14):7709-12
  • Wendel HG, De Stanchina E, Fridman JS, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 2004;428(6980):332-7
  • Jung YD, Nakano K, Liu W, et al. Extracellular signal-regulated kinase activation is required for up-regulation of vascular endothelial growth factor by serum starvation in human colon carcinoma cells. Cancer Res 1999;59(19):4804-7
  • Ellis LM. Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol clin North Am 2004;18(5):1007-21
  • Skinner HD, Zheng JZ, Fang J, et al. Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1alpha, HDM2, and p70S6K1 in response to phosphatidylinositol 3-kinase/AKT signaling. J Biol Chem 2004;279(44):45643-51
  • Han H, Bearss DJ, Browne LW, et al. Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res 2002;62(10):2890-6
  • Coppola D. Molecular prognostic markers in pancreatic cancer. Cancer Control 2000;7(5):421-7
  • Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev 2005;6(8):635-45
  • Baudino TA, McKay C, Pendeville-Samain H, et al. c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev 2002;16(19):2530-43
  • Cheng JQ, Ruggeri B, Klein WM, et al. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 1996;93(8):3636-41
  • Altomare DA, Tanno S, De Rienzo A, et al. Frequent activation of AKT2 kinase in human pancreatic carcinomas. J Cell Biochem 2002;87(4):470-6
  • Repasky GA, Chenette EJ, Der CJ. Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis? Trends Cell Biol 2004;14(11):639-47
  • Asano T, Yao Y, Zhu J, et al. The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-κB and c-Myc in pancreatic cancer cells. Oncogene 2004;23(53):8571-80
  • Ito H, Gardner-Thorpe J, Zinner MJ, et al. Inhibition of tyrosine kinase Src suppresses pancreatic cancer invasiveness. Surgery 2003;134(2):221-6
  • Ram PT, Iyengar R. G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation. Oncogene 2001;20(13):1601-6
  • Trevino JG, Summy JM, Gray MJ, et al. Expression and activity of SRC regulate interleukin-8 expression in pancreatic adenocarcinoma cells: implications for angiogenesis. Cancer Res 2005;65(16):7214-22
  • Caldas C, Hahn SA, Da Costa LT, et al. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 1994;8(1):27-32
  • Schutte M, Hruban RH, Geradts J, et al. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res 1997;57(15):3126-30
  • Yu J, Zhang L. The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun 2005;331(3):851-8
  • Pellegata NS, Sessa F, Renault B, et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res 1994;54(6):1556-60
  • Kretzschmar M, Massague J. SMADs: mediators and regulators of TGF-β signaling. Curr Opin Genet Dev 1998;8(1):103-11
  • Derynck R, Akhurst RJ, Balmain A. TGF-β signaling in tumor suppression and cancer progression. Nat Genet 2001;29(2):117-29
  • Bierie B, Moses HL. Tumour microenvironment: TGF-β: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 2006;6(7):506-20
  • Truty MJ, Urrutia R. Basics of TGF-β and pancreatic cancer. Pancreatology 2007;7(5-6):423-35
  • Zhao S, Venkatasubbarao K, Lazor JW, et al. Inhibition of STAT3Tyr705 phosphorylation by Smad4 suppresses transforming growth factor β-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res 2008;68(11):4221-8
  • Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene 2000;19(21):2607-11
  • Song L, Turkson J, Karras JG, et al. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene 2003;22(27):4150-65
  • Garcia R, Bowman TL, Niu G, et al. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 2001;20(20):2499-513
  • Sato N, Ueki T, Fukushima N, et al. Aberrant methylation of CpG islands in intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology 2002;123(1):365-72
  • Martin ST, Sato N, Dhara S, et al. Aberrant methylation of the human Hedgehog interacting protein (HHIP) gene in pancreatic neoplasms. Cancer biol ther 2005;4(7):728-33
  • Lauth M, Toftgard R. The Hedgehog pathway as a drug target in cancer therapy. Curr Opin Investig Drugs 2007;8(6):457-61
  • Sato N, Maitra A, Fukushima N, et al. Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res 2003;63(14):4158-66
  • Logsdon CD, Simeone DM, Binkley C, et al. Molecular Profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 2003;63(10):2649-57
  • Bardeesy N, Sharpless NE, DePinho RA, Merlino G. The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. Semin Cancer Biol 2001;11(3):201-18
  • Hingorani SR, Petricoin EF, Maitra A, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003;4:437-50
  • Xie K, Wang B, Shi Q, et al. Mouse models of metastatic pancreatic adenocarcinoma. Int J Gastrointest Cancer 2001;29(1):25-36
  • Aguirre AJ, Bardeesy N, Sinha M, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003;17(24):3112-26
  • Brembeck FH, Schreiber FS, Deramaudt TB, et al. The mutant K-ras oncogene causes pancreatic periductal lymphocytic infiltration and gastric mucous neck cell hyperplasia in transgenic mice. Cancer Res 2003;63(9):2005-9
  • Clinicaltrials.gov. National Library of Medicine, National Institues of Health
  • Milella M, Bria E, Cuppone F, et al. Current status of targeted agents (TA) in advanced pancreatic cancer (APC): Meta-analysis of randomized clinical trials (RCT) [abstracts]. ASCO Meeting; 2008 May 20; 2008;26(15 suppl):4637
  • Mendelsohn J. Anti-EGF receptor monoclonal antibodies: biological studies and potential clinical applications. Trans Am Clin Climatol Assoc 1988;100:31-8
  • Bruns CJ, Harbison MT, Davis DW, et al. Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin Cancer Res 2000;6(5):1936-48
  • Xiong HQ, Rosenberg A, LoBuglio A, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter Phase II trial. J Clin Oncol 2004;22(13):2610-6
  • Philip PA, Benedetti J, Fenoglio-Preiser C, et al. Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study ASCO Annual Meeting Proceedings; 2007 Jun 20; 2007. p. LBA4509
  • Maurel J, Martin-Richard M, Conill C, et al. Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2006;66(5):1391-8
  • Czito BG, Willett CG, Bendell JC, et al. Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: Phase I trial results. J Clin Oncol 2006;24(4):656-62
  • Lievre A, Bachet J-B, Le Corre D, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006;66(8):3992-5
  • Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2(1):e17. Published online 25 January 2005, doi:10.1371/journal.pmed.0020017
  • Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005;23(25):5900-9
  • Khambata-Ford S, Garrett CR, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 2007;25(22):3230-7
  • Cappuzzo F, Varella-Garcia M, Finocchiaro G, et al. Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients. Br J Cancer 2008;99(1):83-9
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285(21):1182-6
  • Buchler P, Reber HA, Roth MM, et al. Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer. Neoplasia 2007;9(2):119-27
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350(23):2335-42
  • Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355(24):2542-50
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357(26):2666-76
  • Seo Y, Baba H, Fukuda T, et al. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 2000;88(10):2239-45
  • Itakura J, Ishiwata T, Friess H, et al. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin Cancer Res 1997;3(8):1309-16
  • Kindler HL, Friberg G, Singh DA, et al. Phase II Trial of Bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 2005;23(31):8033-40
  • Tonra JR, Deevi DS, Corcoran E, et al. Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Clin Cancer Res 2006;12(7 Pt 1):2197-207
  • Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116(6):855-67
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64(19):7099-109
  • Siu LL, Awada A, Takimoto CH, et al. Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res 2006;12(1):144-51
  • Rinehart J, Adjei AA, Lorusso PM, et al. Multicenter Phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol 2004;22(22):4456-62
  • Adjei AA, Cohen RB, Franklin W, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 2008;26(13):2139-46
  • Leboeuf R, Baumgartner JE, Benezra M, et al. BRAF(V600E) mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines. J Clin Endocrinol Metabol 2008;93(6):2194-201
  • Friday BB, Yu CR, Dy GK, et al. BRAF V600E disrupts AZD6244-Induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. Cancer Res 2008;68(15):6145-53
  • Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006;439(7074):358-62
  • Haklai R, Elad-Sfadia G, Egozi Y, Kloog Y. Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice. Cancer Chemother Pharmacol 2008;61(1):89-96
  • End DW, Smets G, Todd AV, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001;61(1):131-7
  • Lobell RB, Omer CA, Abrams MT, et al. Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. Cancer Res 2001;61(24):8758-68
  • Venkatasubbarao K, Choudary A, Freeman JW. Farnesyl transferase inhibitor (R115777)-induced inhibition of STAT3(Tyr705) phosphorylation in human pancreatic cancer cell lines require extracellular signal-regulated kinases. Cancer Res 2005;65(7):2861-71
  • Caponigro F. Farnesyl transferase inhibitors: a major breakthrough in anticancer therapy? Naples, 12 April 2002. Anticancer Drugs 2002;13(8):891-7
  • Macdonald JS, McCoy S, Whitehead RP, et al. A Phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study. Invest New Drugs 2005;23(5):485-7
  • Cohen SJ, Ho L, Ranganathan S, et al. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J Clin Oncol 2003;21(7):1301-6
  • Cox AD, Hisaka MM, Buss JE, Der CJ. Specific isoprenoid modification is required for function of normal, but not oncogenic, Ras protein. MolCell Biol 1992;12(6):2606-15
  • Kato K, Cox AD, Hisaka MM, et al. Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. Proc Natl Acad Sci USA 1992;89(14):6403-7
  • Hess KR, Abbruzzese JL. Matrix metalloproteinase inhibition of pancreatic cancer: matching mechanism of action to clinical trial design. J Clin Oncol 2001;19(15):3445-6
  • Moore MJ, Hamm J, Dancey J, et al. Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2003;21(17):3296-302
  • Trevino JG, Summy JM, Lesslie DP, et al. Inhibition of SRC expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model. Am J Pathol 2006;168(3):962-72
  • Johnson FM, Saigal B, Tran H, Donato NJ. Abrogation of signal transducer and activator of transcription 3 reactivation after Src kinase inhibition results in synergistic antitumor effects. Clin Cancer Res 2007;13(14):4233-44
  • Ito D, Fujimoto K, Mori T, et al. In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancer. Int J Cancer 2006;118(9):2337-43
  • Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005;8(3):179-83
  • Hennessy BT, Smith DL, Ram PT, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005;4(12):988-1004
  • Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5(10):761-72
  • Banerji U, Affolter A, Judson I, et al. BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors. Mol Cancer Ther 2008;7(4):737-9
  • Gaspar NJ, Li L, Kapoun AM, et al. Inhibition of transforming growth factor β signaling reduces pancreatic adenocarcinoma growth and invasiveness. Mol Pharmacol 2007;72(1):152-61
  • Lewis HD, Winter A, Murphy TF, et al. STAT3 inhibition in prostate and pancreatic cancer lines by STAT3 binding sequence oligonucleotides: differential activity between 5′ and 3′ ends. Mol Cancer Ther 2008;7(6):1543-50
  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57-70
  • Ashkenazi A. Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev 2008;19(3-4):325-31
  • Dyer MJ, MacFarlane M, Cohen GM. Barriers to effective TRAIL-targeted therapy of malignancy. J Clin Oncol 2007;25(28):4505-6
  • Kiselyov AS. Targeting the hedgehog signaling pathway with small molecules. Anticancer Agents Med Chem 2006;6(5):445-9

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.