Novel neutralizing hedgehog antibody medi-5304 exhibits antitumor activity by inhibiting paracrine hedgehog signaling

Molecular Cancer Therapeutics

Volumn 13, Issue 2, 2014, Pages 386-398

  Michaud, Neil R ^a   Wang, Youzhen ^a   McEachern, Kristen A ^a   Jordan, Jerold J ^a   Mazzola, Anne Marie ^a   Hernandez, Axel ^a   Jalla, Sanjoo ^b   Chesebrough, Jon W ^b   Hynes, Mark J ^c   Belmonte, Matthew A ^a   Wang, Lidong ^c   Kang, Jaspal S ^d,e   Jovanovic, Jelena ^b   Laing, Naomi ^a   Jenkins, David W ^a   Hurt, Elaine ^b   Liang, Meina ^b   Frantz, Christopher ^b   Robert, E Hollingsworth ^b   Simeone, Diane M ^c   Blakey, David C ^a   Bedian, Vahe ^a   more..

^a ASTRAZENECA   (United Kingdom)

^b MEDIMMUNE   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d Amgen British Columbia   (Canada)

^e Innovative Targeting Solutions   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; MEDI-5304; NEUTRALIZING ANTIBODY; PROTEIN BINDING; SONIC HEDGEHOG PROTEIN;

3T3 CELL LINE; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CANCER STEM CELL; CELL CULTURE; CELL LINE; DRUG EFFECTS; DRUG SCREENING; FEMALE; HT 29 CELL LINE; HUMAN; IMMUNOLOGY; KINETICS; MACACA FASCICULARIS; METABOLISM; MOUSE; NONOBESE DIABETIC MOUSE; PANCREATIC NEOPLASMS; PARACRINE SIGNALING; SCID MOUSE; STROMA CELL; TREATMENT OUTCOME; TUMOR CELL LINE; WISTAR RAT;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTINEOPLASTIC AGENTS; CELL LINE; CELL LINE, TUMOR; CELLS, CULTURED; FEMALE; HEDGEHOG PROTEINS; HT29 CELLS; HUMANS; KINETICS; MACACA FASCICULARIS; MICE; MICE, INBRED C57BL; MICE, INBRED NOD; MICE, SCID; NEOPLASTIC STEM CELLS; NIH 3T3 CELLS; PANCREATIC NEOPLASMS; PARACRINE COMMUNICATION; PROTEIN BINDING; RATS, WISTAR; STROMAL CELLS; TREATMENT OUTCOME; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84894142277     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0420     Document Type: Article

References (49)

1. Borzillo GV, Lippa B. The hedgehog signaling pathway as a target for anticancer drug discovery. Curr Top Med Chem 2005;5:147-57
2. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008;22:2454-72
3. Evangelista M, Tian H, de Sauvage FJ. The hedgehog signaling pathway in cancer. Clin Cancer Res 2006;12:5924-8
4. Teglund S, Toftgard R. Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 2010;1805: 181-208
5. Kar S, Deb M, Sengupta D, Shilpi A, Bhutia SK, Patra SK. Intricacies of hedgehog signaling pathways: a perspective in tumorigenesis. Exp Cell Res 2012;318:1959-72
6. Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003;425: 846-51
7. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004;431:707-12
8. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, et al. A paracrine requirement for hedgehog signalling in cancer. Nature 2008;455:406-10
9. O'Toole SA, Machalek DA, Shearer RF, Millar EK, Nair R, Schofield P, et al. Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer. Cancer Res 2011;71:4002-14
10. Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313-7
11. Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, et al. Hedgehog is an early and latemediator of pancreatic cancer tumorigenesis. Nature 2003;425:851-6
12. Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EH Jr, Scott MP. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science 1997;276:817-21
13. Lee MJ, Hatton BA, Villavicencio EH, Khanna PC, Friedman SD, Ditzler S, et al. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci U S A 2012;109:7859-64
14. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009;324:1457-61
15. McCann CK, Growdon WB, Kulkarni-Datar K, Curley MD, Friel AM, Proctor JL, et al. Inhibition of hedgehog signaling antagonizes serous ovarian cancer growth in a primary xenograft model. PLoS ONE 2011;6:e28077
16. Feldmann G, Fendrich V, McGovern K, Bedja D, Bisht S, Alvarez H, et al. An orally bioavailable small-molecule inhibitor of hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. Mol Cancer Ther 2008;7:2725-35
17. Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H, et al. Suppression of the shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(φ/)p53(/) mice. Cancer Cell 2004;6:229-40
18. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-9
19. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361:1173-8
20. Beachy PA, Hymowitz SG, Lazarus RA, Leahy DJ, Siebold C. Interactions between Hedgehog proteins and their binding partners come into view. Genes Dev 2010;24:2001-12
21. Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 2009;8:806-23
22. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res 2007; 67:1030-7
23. Hwang RF, Moore TT, Hattersley MM, Scarpitti M, Yang B, Devereaux E, et al. Inhibition of the hedgehog pathway targets the tumorassociated stroma in pancreatic cancer. Mol Cancer Res 2012; 10:1147-57
24. Green LL. Antibody engineering via genetic engineering of the mouse: XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J Immunol Methods 1999;231:11-23
25. Maun HR, Wen X, Lingel A, de Sauvage FJ, Lazarus RA, Scales SJ, et al. Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-Active site. J Biol Chem 2010;285:26570-80
26. Ruiz i Altaba A, Mas C, Stecca B. The gli code: an information nexus regulating cell fate, stemness and cancer. Trends Cell Biol 2007; 17:438-47
27. Sasai K, Romer JT, Lee Y, Finkelstein D, Fuller C, McKinnon PJ, et al. Shh pathway activity is down-regulated in cultured medulloblastoma cells: implications for preclinical studies. Cancer Res 2006;66: 4215-22
28. Nakamura T, Aikawa T, Iwamoto-Enomoto M, Iwamoto M, Higuchi Y, Pacifici M, et al. Induction of osteogenic differentiation by hedgehog proteins. Biochem Biophys Res Commun 1997;237:465-9
29. Williams KP, Rayhorn P, Chi-Rosso G, Garber EA, Strauch KL, Horan GS, et al. Functional antagonists of sonic hedgehog reveal the importance of the N terminus for activity. J Cell Sci 1999;112: 4405-14
30. Chen W, Tang T, Eastham-Anderson J, Dunlap D, Alicke B, Nannini M, et al. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells. Proc Natl Acad Sci U S A 2011;108:9589-94
31. Ikram MS, Neill GW, Regl G, Eichberger T, Frischauf AM, Aberger F, et al. GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter. J Invest Dermatol 2004;122:1503-9
32. Rohner A, Spilker ME, Lam JL, Pascual B, Bartkowski D, Li QJ, et al. Effective targeting of hedgehog signaling in a medulloblastoma model with PF-5274857, a potent and selective smoothened antagonist that penetrates the blood-brain barrier. Mol Cancer Ther 2012;11:57-65
33. LoRusso PM, Rudin CM, Reddy JC, Tibes R, Weiss GJ, Borad MJ, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011;17:2502-11
34. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1:313-23
35. Bednar F, Simeone DM. Pancreatic cancer stem cell biology and its therapeutic implications. J Gastroenterol 2011;46:1345-52
36. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by highthroughput screening. Cell 2009;138:645-59
37. Cobourne MT, Sharpe PT. Sonic hedgehog signaling and the developing tooth. Curr Top Dev Biol 2005;65:255-87
38. Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, et al. 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 2009;1:338-51
39. Bailey JM, Swanson BJ, Hamada T, Eggers JP, Singh PK, Caffery T, et al. Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin Cancer Res 2008;14:5995-6004
40. Tian H, Callahan CA, DuPree KJ, Darbonne WC, Ahn CP, Scales SJ, et al. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A 2009; 106:4254-9
41. Huang FT, Zhuan-Sun YX, Zhuang YY, Wei SL, Tang J, Chen WB, et al. Inhibition of hedgehog signaling depresses self-renewal of pancreatic cancer stem cells and reverses chemoresistance. Int J Oncol 2012;41:1707-14
42. Feldmann G, Dhara S, Fendrich V, Bedja D, Beaty R, Mullendore M, et al. Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 2007;67:2187-96
43. Mueller MT, Hermann PC, Witthauer J, Rubio-Viqueira B, Leicht SF, Huber S, et al. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology 2009;137:1102-13
44. Meyers-Needham M, Lewis JA, Gencer S, Sentelle RD, Saddoughi SA, Clarke CJ, et al. Off-target function of the Sonic hedgehog inhibitor cyclopamine in mediating apoptosis via nitric oxide-dependent neutral sphingomyelinase 2/ceramide induction. Mol Cancer Ther 2012;11: 1092-1102
45. Hong SP, Wen J, Bang S, Park S, Song SY. CD44-positive cells are responsible for gemcitabine resistance in pancreatic cancer cells. Int J Cancer 2009;125:2323-31
46. Yao J, An Y, Wie JS, Ji ZL, Lu ZP, Wu JL, et al. Cyclopamine reverts acquired chemoresistance and down-regulates cancer stem cell markers in pancreatic cancer cell lines. SwissMedWkly 2011;141:w13208
47. Hoey T, Yen WC, Axelrod F, Basi J, Donigian L, Dylla S, et al. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell 2009;5:168-77
48. Jimeno A, Feldmann G, Suarez-Gauthier A, Rasheed Z, Solomon A, Zou GM,et al.Adirect pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther 2009;8:310-4
49. McMillan R, Matsui W. Molecular pathways: the hedgehog signaling pathway in cancer. Clin Cancer Res 2012;18:4883-8.