A comprehensive review of the role of the hedgehog pathway and vismodegib in the management of basal cell carcinoma

Current Medical Research and Opinion

Volumn 31, Issue 4, 2015, Pages 743-756

  Erdem, Gökmen Umut ^a   Sendur, Mehmet Ali Nahit ^b   Ozdemir, Nuriye Yildirim ^b   Yazici, Ozan ^a   Zengin, Nurullah ^a  

^a ANKARA TRAINING AND RESEARCH HOSPITAL   (Turkey)

^b Department of Gastroenterology   (Turkey)

Author keywords

Basal cell carcinoma; GDC 0449; Hedgehog pathway; Non melanoma; Vismodegib

Indexed keywords

CISPLATIN DERIVATIVE; SONIC HEDGEHOG PROTEIN; VISMODEGIB; ANILIDE; ANTINEOPLASTIC AGENT; PYRIDINE DERIVATIVE;

ADVANCED CANCER; AGEUSIA; ALOPECIA; ASTHENIA; BASAL CELL CARCINOMA; CANCER PATIENT; CANCER RECURRENCE; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DYSGEUSIA; HUMAN; METASTASIS; MUSCLE SPASM; OVERALL SURVIVAL; PATIENT COMPLIANCE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; REVIEW; SIDE EFFECT; SOLID TUMOR; TREATMENT RESPONSE; VOMITING; ANIMAL; CARCINOMA, BASAL CELL; DISEASE FREE SURVIVAL; METABOLISM; PATHOLOGY; SKIN NEOPLASMS;

ANILIDES; ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, BASAL CELL; DISEASE-FREE SURVIVAL; HEDGEHOG PROTEINS; HUMANS; PYRIDINES; SKIN NEOPLASMS;

EID: 84926339483     PISSN: 03007995     EISSN: 14734877     Source Type: Journal    
DOI: 10.1185/03007995.2015.1018988     Document Type: Review

References (99)

1. Wong CS, Strange RC, Lear JT. Basal cell carcinoma. BMJ 2003;327:794-8
2. Crowson AN. Basal cell carcinoma: biology, morphology and clinical implications. Mod Pathol 2006;19(Suppl 2):S127-47
3. Jacob A. Observations respecting an ulcer of peculiar character, which attacks the eyelids and other parts of the face. Dublin Hosp Rep Commun Med Surg 1827;4:232-9
4. Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 2010;146:283-7
5. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med 2005;353:2262-9
6. National Cancer Institute, Surveillance Epidemiology and End Results (SEER) SEER stat fact sheets: Other non-epithelial skin. Available at: http://www.seer.cancer.gov/statfacts/html/othskin.html. [Last accessed 28 February 2012]
7. Skin Cancer Foundation Skin cancer facts. Available at: http://www. skincancer.org/skin-cancer-information/skin-cancer-facts. [Last accessed 27 February 2012]
8. Marks R, Staples M, Giles GG. Trends in non-melanocytic skin cancer treated in Australia: the second national survey. Int J Canc 1993;53:585-90
9. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol 1995;131:157-63
10. Lear JT, Tan BB, Smith AG, et al. Risk factors for basal cell carcinoma in the UK: case-control study in 806 patients. J Roy Soc Med 1997;90:371-4
11. American Academy of Dermatology. Skin cancer: Who gets and causes. 2012. Available at: http://www.aad.org/skin-conditions/dermatology-a-to-z/skin-cancer/whogets-causes. [Last accessed 27 February 2012]
12. Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician 2004;70:1481-8
13. Lear JT, Smith AG. Basal cell carcinoma. Postgrad Med J 1997;73:538-42
14. Parren LJ, Frank J. Hereditary tumour syndromes featuring basal cell carcinomas. Br J Dermatol 2011;165:30-4
15. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Basal cell and squamous cell skin cancers, Version 1.2012. Available at: www.nccn.org/professionals/physician-gls/pdf/ nmsc.pdf [Last accessed 27 February 2012]
16. Walling HW, Fosko SW, Geraminejad PA, et al. Aggressive basal cell carcinoma: presentation, pathogenesis, and management. Canc Metastasis Rev 2004;23:389-402
17. Neville JA, Welch E, Leffell DJ. Management of nonmelanoma skin cancer in 2007. Nature Clin Pract Oncol 2007;4:462-9
18. Weiss GJ, Korn RL. Metastatic basal cell carcinoma in the era of hedgehog signaling pathway inhibitors. Cancer 2012;118:5310-19
19. Snow SN, Sahl W, Lo JS, et al. Metastatic basal cell carcinoma. Report of five cases. Cancer 1994;73:328-35
20. Sitz KV, Keppen M, Johnson DF. Metastatic basal cell carcinoma in acquired immunodeficiency syndrome-related complex. JAMA 1987;257:340-3
21. Wadhera A, Fazio M, Bricca G, Stanton O. Metastatic basal cell carcinoma: a case report and literature review. How accurate is our incidence data?Dermatol Online J 2006;12:7-11
22. Raszewski RL, Guyuron B. Long-term survival following nodal metastases from basal cell carcinoma. Ann Plastic Surg 1990;24:170-5
23. Thissen MR, Neumann MH, Schouten LJ. A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 1999; 135:1177-83
24. Pfeiffer P, Hansen O, Rose C. Systemic cytotoxic therapy of basal cell carcinoma. A review of the literature. Eur J Cancer 1990;26:73-7
25. Kovarik CL, Stewart D, Barnard JJ. Lethal basal cell carcinoma secondary to cerebral invasion. J Am Acad Dermatol 2005;52:149-51
26. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Canc 2008;8:743-54
27. Xie J, Murone M, Luoh SM, et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature 1998;391:90-2
28. Rubin LL, de Sauvage FJ. Targeting the hedgehog pathway in cancer. Nat Rev Drug Discov 2006;5:1026-33
29. Williams JA. Hedgehog signaling pathway as a target for therapeutic intervention in basal cell carcinoma. Drug News Perspect 2003;16: 657-62
30. Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of hedgehog signaling by direct binding of cyclopamine to smoothened. Genes Dev 2002; 16:2743-8
31. Binns W, James LF, Shupe JL, Everett G. A congenital cyclopian-type malformation in lambs induced by maternal ingestion of a range plant, veratrum californicum. Am J Vet Res 1963;24:1164-75
32. Lauth M, Bergstrom A, Shimokawa T, Toftgard R. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci USA 2007;104:8455-60
33. Heretsch P, Tzagkaroulaki L, Giannis A. Modulators of the hedgehog signaling pathway. Bioorg Med Chem 2010;18:6613-24
34. Gupta S, Takebe N, Lorusso P. Targeting the hedgehog pathway in cancer. Ther Adv Med Oncol 2010;2:237-50
35. Merchant JL. Hedgehog signalling in gut development, physiology and cancer. J Physiol 2012;590:421-32
36. Tang JY, So PL, Epstein Jr EH. Novel hedgehog pathway targets against basal cell carcinoma. Toxicol Appl Pharmacol 2007;224:257-64
37. Merchant AA, Matsui W. Targeting hedgehog - a cancer stem cell pathway. Clin Cancer Res 2010;16:3130-40
38. Barakat MT, Humke EW, Scott MP. Learning from Jekyll to control Hyde: hedgehog signaling in development and cancer. Trends Mol Med 2010;16:337-48
39. Hegde GV, Munger CM, Emanuel K, et al. Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma. Mol Cancer Ther 2008;7:1450-60
40. Hegde GV, Peterson KJ, Emanuel K, et al. Hedgehog-induced survival of B-cell chronic lymphocytic leukemia cells in a stromal cell microenvironment: a potential new therapeutic target. Mol Cancer Res 2008;6:1928-36
41. Dierks C, Grbic J, Zirlik K, et al. Essential role of stromally induced hedgehog signaling in B-cell malignancies. Nat Med 2007;13:944-51
42. Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003;425:846-51
43. Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313-17
44. Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004;431:707-12
45. Fan L, Pepicelli CV, Dibble CC, et al. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology 2004;145:3961-70
46. Vorechovsky I, Benediktsson KP, Toftgard R. The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations. Eur J Cancer 1999;35:711-13
47. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 2010;11:331-44
48. Plotnikova OV, Golemis EA, Pugacheva EN. Cell cycle-dependent ciliogenesis and cancer. Canc Res 2008;68:2058-61
49. Rohatgi R, Milenkovic L, Scott MP. Patched1 regulates hedgehog signaling at the primary cilium. Science 2007;317:372-6
50. Taipale J, Beachy PA. The hedgehog and Wnt signalling pathways in cancer. Nature 2001;411:349-54
51. Zardawi SJ, O'Toole SA, Sutherland RL, Musgrove EA. Dysregulation of Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histol Histopathol 2009;24:385-98
52. Corbit KC, Aanstad P, Singla V, et al. Vertebrate smoothened functions at the primary cilium. Nature 2005;437:1018-21
53. Huangfu D, Anderson KV. Cilia and hedgehog responsiveness in the mouse. Proc Natl Acad Sci USA 2005;102:11325-30
54. Huangfu D, Liu A, Rakeman AS, et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 2003;426:83-7
55. Erivedge (vismodegib), prescribing information. South San Francisco, Calif.: Genentech; January 2012. Available at: http://www.gene.com/gene/ products/information/erivedge/pdf/erivedge-prescribing.pdf. [Last accessed 22 February 2012]
56. Scales SJ, de Sauvage FJ. Mechanisms of hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 2009;30:303-12
57. Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996;85:841-51
58. Low JA, de Sauvage FJ. Clinical experience with hedgehog pathway inhibitors. J Clin Oncol 2010;28:5321-6
59. Wong H, Alicke B, West KA, et al. Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent hedgehog pathway activation. Clin Cancer Res 2011;17:4682-92
60. Graham RA, Hop CE, Borin MT, et al. Single and multiple dose intravenous and oral pharmacokinetics of the hedgehog pathway inhibitor vismodegib in healthy female subjects. Br J Clin Pharmacol 2012;74:788-96
61. Fellner C. Vismodegib (erivedge) for advanced Basal cell carcinoma. P & T: a peer-reviewed journal for formulary management. 2012; 37: 670-82
62. LoRusso PM, Jimeno A, Dy G, et al. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res 2011;17:5774-82
63. LoRusso PM, Piha-Paul SA, Mita M, et al. Co-administration of vismodegib with rosiglitazone or combined oral contraceptive in patients with locally advanced or metastatic solid tumors: a pharmacokinetic assessment of drug-drug interaction potential. Canc Chemother Pharmacol 2013;71:193-202
64. LoRusso PM, Rudin CM, Reddy JC, 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
65. Von Hoff DD, LoRusso PM, Rudin CM, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164-72
66. Grob JJ, Kunstfeld R, Dreno B, et al. Vismodegib, a Hedgehog pathway inhibitor (HPI), in advanced basal cell carcinoma (aBCC): STEVIE study interim analysis in 300 patients. J Clin Oncol 31, 2013 (suppl; abstr 9036)
67. Chang ALS, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol 2014;70:60-9
68. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-19
69. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 2012;366:2180-8
70. Amin SH, Tibes R, Kim JE, Hybarger CP. Hedgehog antagonist GDC-0449 is effective in the treatment of advanced basal cell carcinoma. Laryngoscope 2010;120:2456-9
71. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (aBCC): 18-month update of the pivotal ERIVANCE BCC study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2013;31:abstr 9037
72. Sekulic A, Migden MR, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update (30-month) of the pivotal ERIVANCE BCC study. J Clin Oncol 2014;32(Suppl):abstract 9013
73. Chren MM, Sahay AP, Bertenthal DS, Sen S, Landefeld CS. Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 2007;127:1351-7
74. Lewis KD, Sekulic A, Hauschild A, et al. Vismodegib in the treatment of patients with metastatic basal cell carcinoma (mBCC) and distant metastases: survival in the pivotal phase II and phase I studies. J Clin Oncol 2014;32(Suppl):abstract 9012
75. Sekulic A, Hainsworth JD, Lewis KD, et al. Vismodegib for advanced basal cell carcinoma: duration of response after vismodegib discontinuation and response to vismodegib retreatment upon disease progression. J Clin Oncol 2014;32(Suppl):abstract 9081
76. Mortier L, Saiag P, Leccia MT, et al. A phase II study to assess vismodegib in the neoadjuvant treatment of locally advanced basal cell carcinoma (laBCC): The Vismodegib Neoadjuvant (VISMONEO) study. J Clin Oncol 2014; 34(Suppl):abstract TPS9104
77. Kunstfeld R, Hauschild A, Zloty D, et al. MIKIE: a randomized, double-blind, regimen-controlled, phase II, multicenter study to assess the efficacy and safety of two different vismodegib regimens in patients with multiple basal cell carcinomas. J Clin Oncol 2014;32(Suppl):abstract TPS9121
78. Leiter U, Hillen U, Gutzmer R, et al. A phase II, single-armed, multicenter trial of neoadjuvant vismodegib in patients with large and/or recurrent basal cell carcinoma: NICCI. J Clin Oncol 2014;32(Suppl):abstract TPS9116
79. Kaye SB, Fehrenbacher L, Holloway R, et al. A phase II, randomized, placebocontrolled study of vismodegib as maintenance therapy in patients with ovarian cancer in second or third complete remission. Clin Canc Res 2012;18:6509-18
80. Berlin J, Bendell JC, Hart LL, et al. A randomized phase II trial of vismodegib versus placebo with FOLFOX or FOLFIRI and bevacizumab in patients with previously untreated metastatic colorectal cancer. Clin Cancer Res 2013;19:258-67
81. Catenacci DVT, Bahary N, Nattam SR, et al. Final analysis of a phase IB/ randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): a University of Chicago phase II consortium study. J Clin Oncol 2013;31(Suppl):abstract 4012
82. Cohen JD, Christos PJ, Kindler HL, et al. Vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX for first-line therapy of patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: a New York Cancer Consortium led phase II randomized study. J Clin Oncol 2013;31(Suppl):abstract 4011
83. Belani CP, Dahlberg SE, Rudin CM, et al. Three-arm randomized phase II study of cisplatin and etoposide (CE) versus CE with either vismodegib (V) or cixutumumab (Cx) for patients with extensive stage-small cell lung cancer (ES-SCLC) (ECOG 1508). J Clin Oncol 2013;31(suppl):abstr 7508
84. Rudin CM, Hann CL, Laterra J, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361:1173-8
85. Gajjar AJ, Gururangan S, Qaddoumi IA, et al. A prospective phase II study to determine the efficacy of GDC 0449 (vis-modegib) in adults with recurrent medulloblastoma (MB): a Pediatric Brain Tumor Consortium study (PBTC 25B). J Clin Oncol 2013;31(Suppl):abstract 2035
86. Kool M, Korshunov A, Remke M, et al. Molecular sub-groups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3 and group 4 medulloblastomas. Acta Neuropathol 2012;123:473-84
87. Jesus-Acosta AD, O'Dwyer PJ, Ramanthan RK, et al. A phase II study of vismodegib, a hedgehog (Hh) pathway inhibitor, combined with gemcitabine and nab-paclitaxel (nab-P) in patients (pts) with untreated metastatic pancreatic ductal adenocarcinoma (PDA). J Clin Oncol 2014;32(suppl 3): abstr 257
88. Paladini RD, Saleh J, Qian C, et al. Modulation of hair growth with small molecule agonists of the hedgehog signaling pathway. J Invest Dermatol 2005;125:638-46
89. Teperino R, Amann S, Bayer M, et al. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. Cell 2012;151:414-26
90. Schneider FT, Schanzer A, Czupalla CJ, et al. Sonic hedgehog acts as a negative regulator of {beta}-catenin signaling in the adult tongue epithelium. Am J Pathol 2010;177:404-14
91. Corbett Dooren J, Winslow R. New type of cancer drug gets approval. The Wall Street Journal January 31, 2012 (online). Available at: http://online.wsj. com. Accessed. [Last accessed 29 February 2012]
92. Grogan K. FDA approves Roche's skin cancer drug Erivedge. Pharma Times Online, January 31, 2012. Available at: http://www.pharmatimes.com/article/ 12-01-31/FDA-approves-Roche-s-skin-cancer-drug-Erivedge.aspx. [Last accessed 29 February 2012]
93. Carneiro BA, Watkin WG, Mehta UK, Brockstein BE. Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. Canc Investig 2006;24:396-400
94. Denic S. Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin. Am J Clin Oncol 1999;22:32-4
95. Mehta KS, Mahajan VK, Chauhan PS, et al. Metastatic basal cell carcinoma: a biological continuum of basal cell carcinoma? Case Rep Dermatol Med 2012;2012:157187
96. Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in drosophila. Nature 1980;287:795-801
97. Miller SJ, Grekin RC, Nelson KC, et al. NCCN clinical practice guidelines in oncology: basal cell and squamous cell skin cancers. Version 2.2013. Available at: http://www.nccn.org/professionals/physician-gls/f-guidelines. asp#site [Last accessed 3 September 2013]
98. Metcalfe C, de Sauvage FJ. Hedgehog fights back: mechanisms of acquired resistance against smoothened antagonists. Canc Res 2011;71:5057-61
99. ClinicalTrials.gov. Clinical trials search page. Available at: http://www.clinicaltrials. gov/ct2/home [Last accessed 3 September 2013]