Cooperative Hedgehog-EGFR signaling

Frontiers in Bioscience

Volumn 17, Issue 1, 2012, Pages 90-99

  Mangelberger, Doris ^a   Kern, Daniela ^a   Loipetzberger, Andrea ^a   Eberl, Markus ^a   Aberger, Fritz ^a  

^a UNIVERSITY OF SALZBURG   (Austria)

Author keywords

Cancer; Combination Therapy; Epidermal growth factor receptor; GLI transcription factors; Hedgehog signaling; JUN AP 1 transcription factors; MEK ERK Signaling; Oncogenic Transformation; Review

Indexed keywords

ERINACEIDAE;

EID: 84860338320     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/3917     Document Type: Review

References (81)

1. H Land, LF Parada, RA Weinberg: Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304(5927), 596-602 (1983) (Pubitemid 13035496)
2. HE Ruley: Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature 304(5927), 602-6 (1983) (Pubitemid 13035497)
3. A Strasser, AW Harris, ML Bath, S Cory: Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature 348(6299), 331-3 (1990) (Pubitemid 120029100)
4. D Hanahan, RA Weinberg: The hallmarks of cancer. Cell 100(1), 57-70 (2000) (Pubitemid 30046295)
5. B Vogelstein, KW Kinzler: Cancer genes and the pathways they control. Nat Med 10(8), 789-99 (2004) (Pubitemid 39070849)
6. G Parmigiani, S Boca, J Lin, KW Kinzler, V Velculescu, B Vogelstein: Design and analysis issues in genome-wide somatic mutation studies of cancer. Genomics 93(1), 17-21 (2009)
7. T Sjoblom, S Jones, LD Wood, DW Parsons, J Lin, TD Barber, D Mandelker, RJ Leary, J Ptak, N Silliman, S Szabo, P Buckhaults, C Farrell, P Meeh, SD Markowitz, J Willis, D Dawson, JK Willson, AF Gazdar, J Hartigan, L Wu, C Liu, G Parmigiani, BH Park, KE Bachman, N Papadopoulos, B Vogelstein, KW Kinzler, VE Velculescu: The consensus coding sequences of human breast and colorectal cancers. Science 314(5797), 268-74 (2006) (Pubitemid 44571966)
8. LD Wood, DW Parsons, S Jones, J Lin, T Sjoblom, RJ Leary, D Shen, SM Boca, T Barber, J Ptak, N Silliman, S Szabo, Z Dezso, V Ustyanksky, T Nikolskaya, Y Nikolsky, R Karchin, PA Wilson, JS Kaminker, Z Zhang, R Croshaw, J Willis, D Dawson, M Shipitsin, JK Willson, S Sukumar, K Polyak, BH Park, CL Pethiyagoda, PV Pant, DG Ballinger, AB Sparks, J Hartigan, DR Smith, E Suh, N Papadopoulos, P Buckhaults, SD Markowitz, G Parmigiani, KW Kinzler, VE Velculescu, B Vogelstein: The genomic landscapes of human breast and colorectal cancers. Science 318(5853), 1108-13 (2007) (Pubitemid 350134889)
9. C Greenman, P Stephens, R Smith, GL Dalgliesh, C Hunter, G Bignell, H Davies, J Teague, A Butler, C Stevens, S Edkins, S O'Meara, I Vastrik, EE Schmidt, T Avis, S Barthorpe, G Bhamra, G Buck, B Choudhury, J Clements, J Cole, E Dicks, S Forbes, K Gray, K Halliday, R Harrison, K Hills, J Hinton, A Jenkinson, D Jones, A Menzies, T Mironenko, J Perry, K Raine, D Richardson, R Shepherd, A Small, C Tofts, J Varian, T Webb, S West, S Widaa, A Yates, DP Cahill, DN Louis, P Goldstraw, AG Nicholson, F Brasseur, L Looijenga, BL Weber, YE Chiew, A DeFazio, MF Greaves, AR Green, P Campbell, E Birney, DF Easton, G Chenevix-Trench, MH Tan, SK Khoo, BT Teh, ST Yuen, SY Leung, R Wooster, PA Futreal, MR Stratton: Patterns of somatic mutation in human cancer genomes. Nature 446(7132), 153-8 (2007) (Pubitemid 46398669)
10. RK Thomas, AC Baker, RM Debiasi, W Winckler, T Laframboise, WM Lin, M Wang, W Feng, T Zander, L MacConaill, JC Lee, R Nicoletti, C Hatton, M Goyette, L Girard, K Majmudar, L Ziaugra, KK Wong, S Gabriel, R Beroukhim, M Peyton, J Barretina, A Dutt, C Emery, H Greulich, K Shah, H Sasaki, A Gazdar, J Minna, SA Armstrong, IK Mellinghoff, FS Hodi, G Dranoff, PS Mischel, TF Cloughesy, SF Nelson, LM Liau, K Mertz, MA Rubin, H Moch, M Loda, W Catalona, J Fletcher, S Signoretti, F Kaye, KC Anderson, GD Demetri, R Dummer, S Wagner, M Herlyn, WR Sellers, M Meyerson, LA Garraway: High-throughput oncogene mutation profiling in human cancer. Nat Genet 39(3), 347-51 (2007) (Pubitemid 46328493)
11. HR McMurray, ER Sampson, G Compitello, C Kinsey, L Newman, B Smith, SR Chen, L Klebanov, P Salzman, A Yakovlev, H Land: Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype. Nature 453(7198), 1112-6 (2008) (Pubitemid 351871734)
12. C Nusslein-Volhard, E Wieschaus: Mutations affecting segment number and polarity in Drosophila. Nature 287(5785), 795-801 (1980) (Pubitemid 11214475)
13. M Varjosalo, J Taipale: Hedgehog signaling. J Cell Sci 120(Pt 1), 3-6 (2007) (Pubitemid 46206643)
14. CW Wilson, PT Chuang: Mechanism and evolution of cytosolic Hedgehog signal transduction. Development 137(13), 2079-94 (2010)
15. R Rohatgi, L Milenkovic, RB Corcoran, MP Scott: Hedgehog signal transduction by Smoothened: pharmacologic evidence for a 2-step activation process. Proc Natl Acad Sci U S A 106(9), 3196-201 (2009)
16. R Rohatgi, L Milenkovic, MP Scott: Patched1 regulates hedgehog signaling at the primary cilium. Science 317(5836), 372-6 (2007) (Pubitemid 47106377)
17. SY Wong, AD Seol, PL So, AN Ermilov, CK Bichakjian, EH Epstein, Jr., AA Dlugosz, JF Reiter: Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 15(9), 1055-61 (2009)
18. PA Beachy, SG Hymowitz, RA Lazarus, DJ Leahy, C Siebold: Interactions between Hedgehog proteins and their binding partners come into view. Genes Dev 24(18), 2001-12 (2010)
19. PW Ingham, AP McMahon: Hedgehog signaling in animal development: paradigms and principles. Genes Dev 15(23), 3059-87 (2001) (Pubitemid 33115673)
20. J Jiang, CC Hui: Hedgehog signaling in development and cancer. Dev Cell 15(6), 801-12 (2008)
21. M Kasper, G Regl, AM Frischauf, F Aberger: GLI transcription factors: mediators of oncogenic Hedgehog signalling. Eur J Cancer 42(4), 437-45 (2006) (Pubitemid 43227920)
22. R Rohatgi, MP Scott: Patching the gaps in Hedgehog signalling. Nat Cell Biol 9(9), 1005-9 (2007) (Pubitemid 47338138)
23. A Ruiz i Altaba, C Mas B Stecca: The Gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol 17(9), 438-47 (2007) (Pubitemid 47505310)
24. MS Ikram, GW Neill, G Regl, T Eichberger, AM Frischauf, F Aberger, A Quinn, M Philpott: GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. J Invest Dermatol 122(6), 1503-9 (2004) (Pubitemid 38757234)
25. S Teglund, R Toftgard: Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 1805(2), 181-208 (2010)
26. A Ruiz i Altaba, P Sanchez, N Dahmane: Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer 2(5), 361-72 (2002) (Pubitemid 37328949)
27. M Pasca di Magliano, M Hebrok: Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 3(12), 903-11 (2003) (Pubitemid 37500175)
28. EH Epstein: Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 8(10), 743-54 (2008)
29. PA Beachy, SS Karhadkar, DM Berman: Tissue repair and stem cell renewal in carcinogenesis. Nature 432(7015), 324-31 (2004) (Pubitemid 39551660)
30. SJ Scales, FJ de Sauvage: Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 30(6), 303-12 (2009)
31. MD Taylor, L Liu, C Raffel, CC Hui, TG Mainprize, X Zhang, R Agatep, S Chiappa, L Gao, A Lowrance, A Hao, AM Goldstein, T Stavrou, SW Scherer, WT Dura, B Wainwright, JA Squire, JT Rutka, D Hogg: Mutations in SUFU predispose to medulloblastoma. Nat Genet 31(3), 306-10 (2002)
32. H Hahn, C Wicking, PG Zaphiropoulous, MR Gailani, S Shanley, A Chidambaram, I Vorechovsky, E Holmberg, AB Unden, S Gillies, K Negus, I Smyth, C Pressman, DJ Leffell, B Gerrard, AM Goldstein, M Dean, R Toftgard, G Chenevix-Trench, B Wainwright, AE Bale: Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85(6), 841-51 (1996) (Pubitemid 26192135)
33. RL Johnson, AL Rothman, J Xie, LV Goodrich, JW Bare, JM Bonifas, AG Quinn, RM Myers, DR Cox, EH Epstein, Jr., MP Scott: Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272(5268), 1668-71 (1996) (Pubitemid 26200029)
34. AM Snijders, BL Schmidt, J Fridlyand, N Dekker, D Pinkel, RC Jordan, DG Albertson: Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma. Oncogene 24(26), 4232-42 (2005) (Pubitemid 40961777)
35. KW Kinzler, SH Bigner, DD Bigner, JM Trent, ML Law, SJ O'Brien, AJ Wong, B Vogelstein: Identification of an amplified, highly expressed gene in a human glioma. Science 236(4797), 70-3 (1987) (Pubitemid 17056814)
36. J Xie, M Murone, SM Luoh, A Ryan, Q Gu, C Zhang, JM Bonifas, CW Lam, M Hynes, A Goddard, A Rosenthal, EH Epstein, Jr., FJ de Sauvage: Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391(6662), 90-2 (1998) (Pubitemid 28079221)
37. RJ Gorlin: Nevoid basal cell carcinoma syndrome. Dermatol Clin 13(1), 113-25 (1995)
38. RJ Gorlin: Nevoid basal-cell carcinoma syndrome. Medicine (Baltimore) 66(2), 98-113 (1987) (Pubitemid 17059640)
39. RL Yauch, SE Gould, SJ Scales, T Tang, H Tian, CP Ahn, D Marshall, L Fu, T Januario, D Kallop, M Nannini-Pepe, K Kotkow, JC Marsters, LL Rubin, FJ de Sauvage: A paracrine requirement for hedgehog signalling in cancer. Nature 455(7211), 406-10 (2008)
40. C Dierks, J Grbic, K Zirlik, R Beigi, NP Englund, GR Guo, H Veelken, M Engelhardt, R Mertelsmann, JF Kelleher, P Schultz, M Warmuth: Essential role of stromally induced hedgehog signaling in B-cell malignancies. Nat Med 13(8), 944-51 (2007) (Pubitemid 47222041)
41. F Varnat, A Duquet, M Malerba, M Zbinden, C Mas, P Gervaz, A Ruiz i Altaba: Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 1(6-7), 338-51 (2009)
42. C Dierks, R Beigi, GR Guo, K Zirlik, MR Stegert, P Manley, C Trussell, A Schmitt-Graeff, K Landwerlin, H Veelken, M Warmuth: Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell 14(3), 238-49 (2008)
43. V Clement, P Sanchez, N de Tribolet, I Radovanovic, A Ruiz i Altaba: HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 17(2), 165-72 (2007) (Pubitemid 46107823)
44. C Zhao, A Chen, CH Jamieson, M Fereshteh, A Abrahamsson, J Blum, HY Kwon, J Kim, JP Chute, D Rizzieri, M Munchhof, T Vanarsdale, PA Beachy, T Reya: Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature (2009)
45. CM Rudin, CL Hann, J Laterra, RL Yauch, CA Callahan, L Fu, T Holcomb, J Stinson, SE Gould, B Coleman, PM LoRusso, DD Von Hoff, FJ de Sauvage, JA Low: Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361(12), 1173-8 (2009)
46. DD Von Hoff, PM LoRusso, CM Rudin, JC Reddy, RL Yauch, R Tibes, GJ Weiss, MJ Borad, CL Hann, JR Brahmer, HM Mackey, BL Lum, WC Darbonne, JC Marsters, Jr., FJ de Sauvage, JA Low: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361(12), 1164-72 (2009)
47. RL Yauch, GJ Dijkgraaf, B Alicke, T Januario, CP Ahn, T Holcomb, K Pujara, J Stinson, CA Callahan, T Tang, JF Bazan, Z Kan, S Seshagiri, CL Hann, SE Gould, JA Low, CM Rudin, FJ de Sauvage: Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma. Science (2009)
48. S Buonamici, J Williams, M Morrissey, A Wang, R Guo, A Vattay, K Hsiao, J Yuan, J Green, B Ospina, Q Yu, L Ostrom, P Fordjour, DL Anderson, JE Monahan, JF Kelleher, S Peukert, S Pan, X Wu, SM Maira, C Garcia-Echeverria, KJ Briggs, DN Watkins, YM Yao, C Lengauer, M Warmuth, WR Sellers, M Dorsch: Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2(51), 51ra70 (2010)
49. B Stecca, IAA Ruiz: Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol 2(2), 84-95 (2010)
50. M Lauth, R Toftgard: Non-canonical activation of GLI transcription factors: implications for targeted anti-cancer therapy. Cell Cycle 6(20), 2458-63 (2007) (Pubitemid 350058663)
51. NA Riobo, K Lu, CP Emerson, Jr.: Hedgehog signal transduction: signal integration and cross talk in development and cancer. Cell Cycle 5(15), 1612-5 (2006) (Pubitemid 44285246)
52. Y Yarden, MX Sliwkowski: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2(2), 127-37 (2001) (Pubitemid 33674041)
53. NE Hynes, HA Lane: ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5), 341-54 (2005) (Pubitemid 40637826)
54. J Schlessinger: Cell signaling by receptor tyrosine kinases. Cell 103(2), 211-25 (2000)
55. M Sibilia, R Kroismayr, BM Lichtenberger, A Natarajan, M Hecking, M Holcmann: The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 75(9), 770-87 (2007) (Pubitemid 350086174)
56. G Pines, WJ Kostler, Y Yarden: Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy. FEBS Lett 584(12), 2699-706 (2010)
57. JG Paez, PA Janne, JC Lee, S Tracy, H Greulich, S Gabriel, P Herman, FJ Kaye, N Lindeman, TJ Boggon, K Naoki, H Sasaki, Y Fujii, MJ Eck, WR Sellers, BE Johnson, M Meyerson: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304(5676), 1497-500 (2004) (Pubitemid 38720929)
58. TJ Lynch, DW Bell, R Sordella, S Gurubhagavatula, RA Okimoto, BW Brannigan, PL Harris, SM Haserlat, JG Supko, FG Haluska, DN Louis, DC Christiani, J Settleman, DA Haber: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21), 2129-39 (2004) (Pubitemid 38637993)
59. T Mitsudomi, T Kosaka, H Endoh, Y Horio, T Hida, S Mori, S Hatooka, M Shinoda, T Takahashi, Y Yatabe: Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 23(11), 2513-20 (2005) (Pubitemid 47050841)
60. RH Alvarez, V Valero, GN Hortobagyi: Emerging targeted therapies for breast cancer. J Clin Oncol 28(20), 3366-79 (2010)
61. V Palma, DA Lim, N Dahmane, P Sanchez, TC Brionne, CD Herzberg, Y Gitton, A Carleton, A Alvarez-Buylla, A Ruiz i Altaba: Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 132(2), 335-44 (2005) (Pubitemid 40268283)
62. V Palma, A Ruiz i Altaba: Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties in the developing neocortex. Development 131(2), 337-45 (2004) (Pubitemid 38181373)
63. RL Bigelow, EY Jen, M Delehedde, NS Chari, TJ McDonnell: Sonic hedgehog induces epidermal growth factor dependent matrix infiltration in HaCaT keratinocytes. J Invest Dermatol 124(2), 457-65 (2005) (Pubitemid 40175896)
64. M Kasper, H Schnidar, GW Neill, M Hanneder, S Klingler, L Blaas, C Schmid, C Hauser-Kronberger, G Regl, MP Philpott, F Aberger: Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes. Mol Cell Biol 26(16), 6283-98 (2006) (Pubitemid 44204544)
65. H Schnidar, M Eberl, S Klingler, D Mangelberger, M Kasper, C Hauser-Kronberger, G Regl, R Kroismayr, R Moriggl, M Sibilia, F Aberger: Epidermal growth factor receptor signaling synergizes with Hedgehog/GLI in oncogenic transformation via activation of the MEK/ERK/JUN pathway. Cancer Res 69(4), 1284-92 (2009)
66. B Stecca, C Mas, V Clement, M Zbinden, R Correa, V Piguet, F Beermann, IAA Ruiz: Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci U S A 104(14), 5895-900 (2007) (Pubitemid 47175630)
67. NA Riobo, K Lu, X Ai, GM Haines, CP Emerson, Jr.: Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Proc Natl Acad Sci U S A 103(12), 4505-10 (2006)
68. B Ju, J Spitsbergen, CJ Eden, MR Taylor, W Chen: Coactivation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol Cancer 8, 40 (2009)
69. H Greulich, TH Chen, W Feng, PA Janne, JV Alvarez, M Zappaterra, SE Bulmer, DA Frank, WC Hahn, WR Sellers, M Meyerson: Oncogenic transformation by inhibitorsensitive and -resistant EGFR mutants. PLoS Med 2(11), e313 (2005)
70. NA Riobo, GM Haines, CP Emerson, Jr.: Protein kinase C-delta and mitogen-activated protein/extracellular signalregulated kinase-1 control GLI activation in hedgehog signaling. Cancer Res 66(2), 839-45 (2006) (Pubitemid 43165949)
71. M Seto, M Ohta, Y Asaoka, T Ikenoue, M Tada, K Miyabayashi, D Mohri, Y Tanaka, H Ijichi, K Tateishi, F Kanai, T Kawabe, M Omata: Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. Mol Carcinog 48(8), 703-12 (2009)
72. TC Whisenant, DT Ho, RW Benz, JS Rogers, RM Kaake, EA Gordon, L Huang, P Baldi, L Bardwell: Computational prediction and experimental verification of new MAP kinase docking sites and substrates including Gli transcription factors. PLoS Comput Biol 6(8) (2010)
73. PO Hackel, E Zwick, N Prenzel, A Ullrich: Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol 11(2), 184-9 (1999) (Pubitemid 29164032)
74. S Laner-Plamberger, A Kaser, M Paulischta, C Hauser-Kronberger, T Eichberger, AM Frischauf: Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes. Oncogene (2009)
75. M Mimeault, SL Johansson, G Vankatraman, E Moore, JP Henichart, P Depreux, MF Lin, SK Batra: Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells. Mol Cancer Ther 6(3), 967-78 (2007) (Pubitemid 46554566)
76. M Mimeault, E Moore, N Moniaux, JP Henichart, P Depreux, MF Lin, SK Batra: Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells. Int J Cancer 118(4), 1022-31 (2006) (Pubitemid 43157681)
77. M Lauth, A Bergstrom, T Shimokawa, U Tostar, Q Jin, V Fendrich, C Guerra, M Barbacid, R Toftgard: DYRK1Bdependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS. Nat Struct Mol Biol 17(6), 718-25 (2010)
78. O Nolan-Stevaux, J Lau, ML Truitt, GC Chu, M Hebrok, ME Fernandez-Zapico, D Hanahan: GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev 23(1), 24-36 (2009)
79. KP Olive, MA Jacobetz, CJ Davidson, A Gopinathan, D McIntyre, D Honess, B Madhu, MA Goldgraben, ME Caldwell, D Allard, KK Frese, G Denicola, C Feig, C Combs, SP Winter, H Ireland-Zecchini, S Reichelt, WJ Howat, A Chang, M Dhara, L Wang, F Ruckert, R Grutzmann, C Pilarsky, K Izeradjene, SR Hingorani, P Huang, SE Davies, W Plunkett, M Egorin, RH Hruban, N Whitebread, K McGovern, J Adams, C Iacobuzio-Donahue, J Griffiths, DA Tuveson: Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324(5933), 1457-61 (2009)
80. MT Mueller, PC Hermann, J Witthauer, B Rubio-Viqueira, SF Leicht, S Huber, JW Ellwart, M Mustafa, P Bartenstein, JG D'Haese, MH Schoenberg, F Berger, KW Jauch, M Hidalgo, C Heeschen: Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 137(3), 1102-13 (2009)
81. C Li, DG Heidt, P Dalerba, CF Burant, L Zhang, V Adsay, M Wicha, MF Clarke, DM Simeone: Identification of pancreatic cancer stem cells. Cancer Res 67(3), 1030-7 (2007)