Ipilimumab and Vemurafenib: Two different routes for targeting Melanoma

Current Cancer Drug Targets

Volumn 13, Issue 8, 2013, Pages 879-894

  Burgeiro, Ana ^a,b   Mollinedo, Faustino ^c   Oliveira, Paulo J ^a  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

^c UNIVERSITY OF SALAMANCA   (Spain)

Author keywords

BRAFV600E mutation; Clinical investigation; Immunotherapy; Ipilimumab; Melanoma; Vemurafenib

Indexed keywords

B RAF KINASE; BEVACIZUMAB; BUPARLISIB; CARMUSTINE; CISPLATIN; DABRAFENIB; DACARBAZINE; DOXYCYCLINE; EVEROLIMUS; GLYCOPROTEIN GP 100; HEAT SHOCK PROTEIN 90 INHIBITOR; INTERLEUKIN 2; IPILIMUMAB; KETOCONAZOLE; LEFLUNOMIDE; METFORMIN; MITOGEN ACTIVATED PROTEIN KINASE; PEGINTERFERON ALPHA2B; PLACEBO; RECOMBINANT INTERLEUKIN 2; RIFAMPICIN; SELUMETINIB; TAMOXIFEN; TAXANE DERIVATIVE; TEMOZOLOMIDE; TICILIMUMAB; TRAMETINIB; UNINDEXED DRUG; VEMURAFENIB; VINCA ALKALOID;

ALOPECIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; CANCER GROWTH; CANCER SURVIVAL; COLITIS; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; FATIGUE; GASTROINTESTINAL SYMPTOM; GENE MUTATION; HUMAN; IMMUNOPATHOLOGY; KERATOACANTHOMA; MELANOMA; METASTATIC MELANOMA; MULTICENTER STUDY (TOPIC); MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PHOTOSENSITIVITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECOMMENDED DRUG DOSE; SIGNAL TRANSDUCTION; SKIN DISEASE; SQUAMOUS CELL CARCINOMA;

ANIMALS; ANTIBODIES, MONOCLONAL; HUMANS; INDOLES; MELANOMA; SIGNAL TRANSDUCTION; SULFONAMIDES;

EID: 84888109114     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/15680096113139990080     Document Type: Article

References (92)

1. Shoo, B. A.; Kashani-Sabet, M. Melanoma arising in African-, Asian-, Latino-and Native-American populations. Semin. Cutan. Med. Surg. 2009, 28 (2), 96-102.
2. National Cancer Institute, SEER Stat Fact Sheets: Melanoma of the Skin. http://seer. cancer. gov/statfacts/html/melan. html (accessed May 19, 2013).
3. Goldstein, B. G.; Goldstein, A. O. Diagnosis and management of malignant melanoma. Am. Fam. Physician 2001, 63 (7), 1359-1368, 1374.
4. American Cancer Society, Cancer Facts and Figures 2013. 2013.
5. Rubin, K. M.; Lawrence, D. P. Your patient with melanoma: staging, prognosis, and treatment. Oncology (Williston Park) 2009, 23 (8 Suppl), 13-21.
6. Sosman, J. A.; Margolin, K. A. Inside life of melanoma cell signalling, molecular insights, and therapeutic targets. Curr. Oncol. Rep. 2009, 11 (5), 405-411.
7. Hussein, M. R. Genetic pathways to melanoma tumorigenesis. J Clin. Pathol. 2004, 57 (8), 797-801.
8. Hodi, F. S. Well-defined melanoma antigens as progression markers for melanoma: insights into differential expression and host response based on stage. Clin. Cancer Res. 2006, 12 (3 Pt 1), 673-678.
9. Medic, S.; Pearce, R. L.; Heenan, P. J.; Ziman, M. Molecular markers of circulating melanoma cells. Pigment Cell. Res. 2007, 20 (2), 80-91.
10. Tsao, H.; Atkins, M. B.; Sober, A. J. Management of cutaneous melanoma. N. Engl. J. Med. 2004, 351 (10), 998-1012.
11. McMasters, K. M.; Sondak, V. K.; Lotze, M. T.; Ross, M. I. Recent advances in melanoma staging and therapy. Ann. Surg. Oncol. 1999, 6 (5), 467-475.
12. Creagan, E. T. Malignant melanoma: an emerging and preventable medical catastrophe. Mayo. Clin. Proc. 1997, 72 (6), 570-574.
13. Hocker, T. L.; Singh, M. K.; Tsao, H. Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside. J. Invest. Dermatol. 2008, 128 (11), 2575-2595.
14. Danson, S.; Lorigan, P.; Arance, A.; Clamp, A.; Ranson, M.; Hodgetts, J.; Lomax, L.; Ashcroft, L.; Thatcher, N.; Middleton, M. R. Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma. J. Clin. Oncol. 2003, 21 (13), 2551-2557.
15. Boogerd, W.; de Gast, G. C.; Dalesio, O. Temozolomide in advanced malignant melanoma with small brain metastases: can we withhold cranial irradiation? Cancer 2007, 109 (2), 306-312.
16. Seetharamu, N.; Ott, P. A.; Pavlick, A. C. Novel therapeutics for melanoma. Expert Rev. Anticancer Ther. 2009, 9 (6), 839-849.
17. Kim, C. J.; Dessureault, S.; Gabrilovich, D.; Reintgen, D. S.; Slingluff, C. L., Jr. Immunotherapy for melanoma. Cancer Control 2002, 9 (1), 22-30.
18. Monzon, J. G.; Dancey, J. Targeted agents for the treatment of metastatic melanoma. Onco. Targets Ther. 2012, 5, 31-46.
19. Balch, C. M.; Buzaid, A. C.; Soong, S. J.; Atkins, M. B.; Cascinelli, N.; Coit, D. G.; Fleming, I. D.; Gershenwald, J. E.; Houghton, A., Jr.; Kirkwood, J. M.; McMasters, K. M.; Mihm, M. F.; Morton, D. L.; Reintgen, D. S.; Ross, M. I.; Sober, A.; Thompson, J. A.; Thompson, J. F. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J. Clin. Oncol. 2001, 19 (16), 3635-3648.
20. Jemal, A.; Bray, F.; Center, M. M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA. Cancer J. Clin. 2011, 61 (2), 69-90.
21. Fonkem, E.; Uhlmann, E. J.; Floyd, S. R.; Mahadevan, A.; Kasper, E.; Eton, O.; Wong, E. T. Melanoma brain metastasis: overview of current management and emerging targeted therapies. Expert. Rev. Neurother. 2012, 12 (10), 1207-1215.
22. Atkins, M. B.; Kunkel, L.; Sznol, M.; Rosenberg, S. A. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J. Sci. Am. 2000, 6 Suppl. 1, S11-S14.
23. Jeter, J. M.; Cranmer, L. D.; Hersh, E. M. Ipilimumab pharmacotherapy in patients with metastatic melanoma. Clin. Med. Insights Oncol. 2012, 6, 275-286.
24. Bruggemann, M.; Williams, G. T.; Bindon, C. I.; Clark, M. R.; Walker, M. R.; Jefferis, R.; Waldmann, H.; Neuberger, M. S. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J. Exp. Med. 1987, 166 (5), 1351-1361.
25. Tarhini, A. A. Tremelimumab: a review of development to date in solid tumors. Immunotherapy 2013, 5 (3), 215-229.
26. Ribas, A.; Kefford, R.; Marshall, M. A.; Punt, C. J.; Haanen, J. B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K. L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G. A.; Dreno, B.; Nathan, P. D.; Mackiewicz, J.; Kirkwood, J. M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J. Clin. Oncol. 2013, 31 (5), 616-622.
27. Ribas, A. Clinical development of the anti-CTLA-4 antibody tremelimumab. Semin. Oncol. 2010, 37 (5), 450-454.
28. Egen, J. G.; Kuhns, M. S.; Allison, J. P. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat. Immunol. 2002, 3 (7), 611-618.
29. Hodi, F. S.; O'Day, S. J.; McDermott, D. F.; Weber, R. W.; Sosman, J. A.; Haanen, J. B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J. C.; Akerley, W.; van den Eertwegh, A. J.; Lutzky, J.; Lorigan, P.; Vaubel, J. M.; Linette, G. P.; Hogg, D.; Ottensmeier, C. H.; Lebbe, C.; Peschel, C.; Quirt, I.; Clark, J. I.; Wolchok, J. D.; Weber, J. S.; Tian, J.; Yellin, M. J.; Nichol, G. M.; Hoos, A.; Urba, W. J. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 2010, 363 (8), 711-723.
30. Robert, C.; Thomas, L.; Bondarenko, I.; O'Day, S.; M, D. J.; Garbe, C.; Lebbe, C.; Baurain, J. F.; Testori, A.; Grob, J. J.; Davidson, N.; Richards, J.; Maio, M.; Hauschild, A.; Miller, W. H., Jr.; Gascon, P.; Lotem, M.; Harmankaya, K.; Ibrahim, R.; Francis, S.; Chen, T. T.; Humphrey, R.; Hoos, A.; Wolchok, J. D. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 2011, 364 (26), 2517-2526.
31. O'Day, S. J.; Maio, M.; Chiarion-Sileni, V.; Gajewski, T. F.; Pehamberger, H.; Bondarenko, I. N.; Queirolo, P.; Lundgren, L.; Mikhailov, S.; Roman, L.; Verschraegen, C.; Humphrey, R.; Ibrahim, R.; de Pril, V.; Hoos, A.; Wolchok, J. D. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann. Oncol. 2010, 21 (8), 1712-1717.
32. Wolchok, J. D.; Neyns, B.; Linette, G.; Negrier, S.; Lutzky, J.; Thomas, L.; Waterfield, W.; Schadendorf, D.; Smylie, M.; Guthrie, T., Jr.; Grob, J. J.; Chesney, J.; Chin, K.; Chen, K.; Hoos, A.; O'Day, S. J.; Lebbe, C. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet. Oncol. 2010, 11 (2), 155-164.
33. Di Giacomo, A. M.; Danielli, R.; Guidoboni, M.; Calabro, L.; Carlucci, D.; Miracco, C.; Volterrani, L.; Mazzei, M. A.; Biagioli, M.; Altomonte, M.; Maio, M. Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases. Cancer Immunol. Immunother. 2009, 58 (8), 1297-1306.
34. Revicki, D. A.; van den Eertwegh, A. J.; Lorigan, P.; Lebbe, C.; Linette, G.; Ottensmeier, C. H.; Safikhani, S.; Messina, M.; Hoos, A.; Wagner, S.; Kotapati, S. Health related quality of life outcomes for unresectable stage III or IV melanoma patients receiving ipilimumab treatment. Health Qual. Life Outcomes 2012, 10, 66.
35. Hersh, E. M.; O'Day, S. J.; Powderly, J.; Khan, K. D.; Pavlick, A. C.; Cranmer, L. D.; Samlowski, W. E.; Nichol, G. M.; Yellin, M. J.; Weber, J. S. A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naive patients with advanced melanoma. Invest. New Drugs 2011, 29 (3), 489-498.
36. Wolchok, J. How recent advances in immunotherapy are changing the standard of care for patients with metastatic melanoma. Ann. Oncol. 2012, 23 Suppl 8, viii15-21.
37. Robert, C.; Schadendorf, D.; Messina, M.; Hodi, F. S.; O'Day, S. Efficacy and safety of retreatment with ipilimumab in patients with pretreated advanced melanoma who progressed after initially achieving disease control. Clin. Cancer Res. 2013, 19 (8), 2232-2239.
38. Assi, H.; Wilson, K. S., Immune toxicities and long remission duration after ipilimumab therapy for metastatic melanoma: two illustrative cases. Curr. Oncol. 2013, 20 (2), e165-e169.
39. Weber, J. S.; Amin, A.; Minor, D.; Siegel, J.; Berman, D.; O'Day, S. J. Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. Melanoma Res. 2011, 21 (6), 530-534.
40. Schartz, N. E.; Farges, C.; Madelaine, I.; Bruzzoni, H.; Calvo, F.; Hoos, A.; Lebbe, C. Complete regression of a previously untreated melanoma brain metastasis with ipilimumab. Melanoma Res. 2010, 20 (3), 247-250.
41. Hodi, F. S.; Oble, D. A.; Drappatz, J.; Velazquez, E. F.; Ramaiya, N.; Ramakrishna, N.; Day, A. L.; Kruse, A.; Mac Rae, S.; Hoos, A.; Mihm, M. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. Nat. Clin. Pract. Oncol. 2008, 5 (9), 557-561.
42. Downey, S. G.; Klapper, J. A.; Smith, F. O.; Yang, J. C.; Sherry, R. M.; Royal, R. E.; Kammula, U. S.; Hughes, M. S.; Allen, T. E.; Levy, C. L.; Yellin, M.; Nichol, G.; White, D. E.; Steinberg, S. M.; Rosenberg, S. A. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin. Cancer Res. 2007, 13 (22 Pt 1), 6681-6688.
43. Mathew, M.; Tam, M.; Ott, P. A.; Pavlick, A. C.; Rush, S. C.; Donahue, B. R.; Golfinos, J. G.; Parker, E. C.; Huang, P. P.; Narayana, A. Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery. Melanoma Res. 2013, 23 (3), 191-195.
44. Margolin, K. Ipilimumab in a Phase II trial of melanoma patients with brain metastases. Oncoimmunology 2012, 1 (7), 1197-1199.
45. Knisely, J. P.; Yu, J. B.; Flanigan, J.; Sznol, M.; Kluger, H. M.; Chiang, V. L. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J. Neurosurg. 2012, 117 (2), 227-233.
46. Margolin, K.; Ernstoff, M. S.; Hamid, O.; Lawrence, D.; McDermott, D.; Puzanov, I.; Wolchok, J. D.; Clark, J. I.; Sznol, M.; Logan, T. F.; Richards, J.; Michener, T.; Balogh, A.; Heller, K. N.; Hodi, F. S. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet. Oncol. 2012, 13 (5), 459-465.
47. Maio, M.; Di Giacomo, A. M.; Robert, C.; Eggermont, A. M. Update on the role of ipilimumab in melanoma and first data on new combination therapies. Curr. Opin. Oncol. 2013, 25 (2), 166-72.
48. Korman, J. B.; Fisher, D. E., Developing melanoma therapeutics: overview and update. Wiley Interdiscip. Rev. Syst. Biol. Med. 2013, 5 (3), 257-271.
49. Weber, J. S.; Kahler, K. C.; Hauschild, A. Management of immune-related adverse events and kinetics of response with ipilimumab. J. Clin. Oncol. 2012, 30 (21), 2691-2697.
50. Jazirehi, A. R.; Wenn, P. B.; Damavand, M. Therapeutic implications of targeting the PI3Kinase/AKT/mTOR signalling module in melanoma therapy. Am. J. Cancer. Res. 2012, 2 (2), 178-191.
51. Platz, A.; Egyhazi, S.; Ringborg, U.; Hansson, J. Human cutaneous melanoma; a review of NRAS and BRAF mutation frequencies in relation to histogenetic subclass and body site. Mol. Oncol. 2008, 1 (4), 395-405.
52. Cohen, C.; Zavala-Pompa, A.; Sequeira, J. H.; Shoji, M.; Sexton, D. G.; Cotsonis, G.; Cerimele, F.; Govindarajan, B.; Macaron, N.; Arbiser, J. L. Mitogen-actived protein kinase activation is an early event in melanoma progression. Clin. Cancer Res. 2002, 8 (12), 3728-3733.
53. Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M. J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B. A.; Cooper, C.; Shipley, J.; Hargrave, D.; Pritchard-Jones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G. J.; Bigner, D. D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J. W.; Leung, S. Y.; Yuen, S. T.; Weber, B. L.; Seigler, H. F.; Darrow, T. L.; Paterson, H.; Marais, R.; Marshall, C. J.; Wooster, R.; Stratton, M. R.; Futreal, P. A., Mutations of the BRAF gene in human cancer. Nature 2002, 417 (6892), 949-954.
54. Wan, P. T.; Garnett, M. J.; Roe, S. M.; Lee, S.; Niculescu-Duvaz, D.; Good, V. M.; Jones, C. M.; Marshall, C. J.; Springer, C. J.; Barford, D.; Marais, R., Mechanism of activation of the RAF-ERK signalling pathway by oncogenic mutations of B-RAF. Cell 2004, 116 (6), 855-867.
55. Dhomen, N.; Marais, R., BRAF signalling and targeted therapies in melanoma. Hematol. Oncol. Clin. North. Am. 2009, 23 (3), 529-45, ix.
56. Maurer, G.; Tarkowski, B.; Baccarini, M., Raf kinases in cancerroles and therapeutic opportunities. Oncogene. 2011, 30 (32), 3477-3488.
57. Ascierto, P. A.; Kirkwood, J. M.; Grob, J. J.; Simeone, E.; Grimaldi, A. M.; Maio, M.; Palmieri, G.; Testori, A.; Marincola, F. M.; Mozzillo, N., The role of BRAF V600 mutation in melanoma. J. Transl. Med. 2012, 10, 85.
58. Kolch, W., Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J. 2000, 351 Pt 2, 289-305.
59. Bollag, G.; Hirth, P.; Tsai, J.; Zhang, J.; Ibrahim, P. N.; Cho, H.; Spevak, W.; Zhang, C.; Zhang, Y.; Habets, G.; Burton, E. A.; Wong, B.; Tsang, G.; West, B. L.; Powell, B.; Shellooe, R.; Marimuthu, A.; Nguyen, H.; Zhang, K. Y.; Artis, D. R.; Schlessinger, J.; Su, F.; Higgins, B.; Iyer, R.; D'Andrea, K.; Koehler, A.; Stumm, M.; Lin, P. S.; Lee, R. J.; Grippo, J.; Puzanov, I.; Kim, K. B.; Ribas, A.; McArthur, G. A.; Sosman, J. A.; Chapman, P. B.; Flaherty, K. T.; Xu, X.; Nathanson, K. L.; Nolop, K., Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010, 467 (7315), 596-599.
60. Joseph, E. W.; Pratilas, C. A.; Poulikakos, P. I.; Tadi, M.; Wang, W.; Taylor, B. S.; Halilovic, E.; Persaud, Y.; Xing, F.; Viale, A.; Tsai, J.; Chapman, P. B.; Bollag, G.; Solit, D. B.; Rosen, N., The RAF inhibitor PLX4032 inhibits ERK signalling and tumor cell proliferation in a V600E BRAF-selective manner. Proc. Natl. Acad. Sci. USA 2010, 107 (33), 14903-14908.
61. Poulikakos, P. I.; Zhang, C.; Bollag, G.; Shokat, K. M.; Rosen, N., RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010, 464 (7287), 427-430.
62. Heidorn, S. J.; Milagre, C.; Whittaker, S.; Nourry, A.; Niculescu-Duvas, I.; Dhomen, N.; Hussain, J.; Reis-Filho, J. S.; Springer, C. J.; Pritchard, C.; Marais, R., Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010, 140 (2), 209-221.
63. Lee, J. T.; Li, L.; Brafford, P. A.; van den Eijnden, M.; Halloran, M. B.; Sproesser, K.; Haass, N. K.; Smalley, K. S.; Tsai, J.; Bollag, G.; Herlyn, M., PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas. Pigment Cell Melanoma. Res. 2010, 23 (6), 820-827.
64. Smalley, K. S., PLX-4032, a small-molecule B-Raf inhibitor for the potential treatment of malignant melanoma. Curr. Opin. Investig. Drugs 2010, 11 (6), 699-706.
65. Sondergaard, J. N.; Nazarian, R.; Wang, Q.; Guo, D.; Hsueh, T.; Mok, S.; Sazegar, H.; MacConaill, L. E.; Barretina, J. G.; Kehoe, S. M.; Attar, N.; von Euw, E.; Zuckerman, J. E.; Chmielowski, B.; Comin-Anduix, B.; Koya, R. C.; Mischel, P. S.; Lo, R. S.; Ribas, A., Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032. J. Transl. Med. 2010, 8, 39.
66. Hatzivassiliou, G.; Song, K.; Yen, I.; Brandhuber, B. J.; Anderson, D. J.; Alvarado, R.; Ludlam, M. J.; Stokoe, D.; Gloor, S. L.; Vigers, G.; Morales, T.; Aliagas, I.; Liu, B.; Sideris, S.; Hoeflich, K. P.; Jaiswal, B. S.; Seshagiri, S.; Koeppen, H.; Belvin, M.; Friedman, L. S.; Malek, S., RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010, 464 (7287), 431-435.
67. Halaban, R.; Zhang, W.; Bacchiocchi, A.; Cheng, E.; Parisi, F.; Ariyan, S.; Krauthammer, M.; McCusker, J. P.; Kluger, Y.; Sznol, M. PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells. Pigment Cell Melanoma Res. 2010, 23 (2), 190-200.
68. Chapman, P. B.; Hauschild, A.; Robert, C.; Haanen, J. B.; Ascierto, P.; Larkin, J.; Dummer, R.; Garbe, C.; Testori, A.; Maio, M.; Hogg, D.; Lorigan, P.; Lebbe, C.; Jouary, T.; Schadendorf, D.; Ribas, A.; O'Day, S. J.; Sosman, J. A.; Kirkwood, J. M.; Eggermont, A. M.; Dreno, B.; Nolop, K.; Li, J.; Nelson, B.; Hou, J.; Lee, R. J.; Flaherty, K. T.; McArthur, G. A. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 2011, 364 (26), 2507-2516.
69. Flaherty, K. T.; Puzanov, I.; Kim, K. B.; Ribas, A.; McArthur, G. A.; Sosman, J. A.; O'Dwyer, P. J.; Lee, R. J.; Grippo, J. F.; Nolop, K.; Chapman, P. B. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 2010, 363 (9), 809-819.
70. Sosman, J. A.; Kim, K. B.; Schuchter, L.; Gonzalez, R.; Pavlick, A. C.; Weber, J. S.; McArthur, G. A.; Hutson, T. E.; Moschos, S. J.; Flaherty, K. T.; Hersey, P.; Kefford, R.; Lawrence, D.; Puzanov, I.; Lewis, K. D.; Amaravadi, R. K.; Chmielowski, B.; Lawrence, H. J.; Shyr, Y.; Ye, F.; Li, J.; Nolop, K. B.; Lee, R. J.; Joe, A. K.; Ribas, A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N. Engl. J. Med. 2012, 366 (8), 707-714.
71. Vultur, A.; Villanueva, J.; Herlyn, M. Targeting BRAF in advanced melanoma: a first step toward manageable disease. Clin. Cancer Res. 2011, 17 (7), 1658-1663.
72. Young, K.; Minchom, A.; Larkin, J. BRIM-1,-2 and-3 trials: improved survival with vemurafenib in metastatic melanoma patients with a BRAF(V600E) mutation. Future Oncol. 2012, 8 (5), 499-507.
73. Keating, G. M. Vemurafenib: in unresectable or metastatic melanoma. BioDrugs 2012, 26 (5), 325-334.
74. Ravnan, M. C.; Matalka, M. S. Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma. Clin. Ther. 2012, 34 (7), 1474-1486.
75. Shah, N.; Iyer, R. M.; Mair, H. J.; Choi, D. S.; Tian, H.; Diodone, R.; Fahnrich, K.; Pabst-Ravot, A.; Tang, K.; Scheubel, E.; Grippo, J. F.; Moreira, S. A.; Go, Z.; Mouskountakis, J.; Louie, T.; Ibrahim, P. N.; Sandhu, H.; Rubia, L.; Chokshi, H.; Singhal, D.; Malick, W. Improved human bioavailability of vemurafenib, a practically insoluble drug, using an amorphous polymer-stabilized solid dispersion prepared by a solvent-controlled coprecipitation process. J. Pharm. Sci. 2013, 102 (3), 967-981.
76. Rochet, N. M.; Kottschade, L. A.; Markovic, S. N. Vemurafenib for melanoma metastases to the brain. N. Engl. J. Med. 2011, 365 (25), 2439-2441.
77. Rochet, N. M.; Dronca, R. S.; Kottschade, L. A.; Chavan, R. N.; Gorman, B.; Gilbertson, J. R.; Markovic, S. N. Melanoma brain metastases and vemurafenib: need for further investigation. Mayo Clin. Proc. 2012, 87 (10), 976-981.
78. Solit, D.; Sawyers, C. L. Drug discovery: How melanomas bypass new therapy. Nature 2010, 468 (7326), 902-903.
79. Trunzer, K.; Pavlick, A. C.; Schuchter, L.; Gonzalez, R.; McArthur, G. A.; Hutson, T. E.; Moschos, S. J.; Flaherty, K. T.; Kim, K. B.; Weber, J. S.; Hersey, P.; Long, G. V.; Lawrence, D.; Ott, P. A.; Amaravadi, R. K.; Lewis, K. D.; Puzanov, I.; Lo, R. S.; Koehler, A.; Kockx, M.; Spleiss, O.; Schell-Steven, A.; Gilbert, H. N.; Cockey, L.; Bollag, G.; Lee, R. J.; Joe, A. K.; Sosman, J. A.; Ribas, A. Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J. Clin. Oncol. 2013, 31 (14), 1767-1774.
80. Corcoran, R. B.; Settleman, J.; Engelman, J. A. Potential therapeutic strategies to overcome acquired resistance to BRAF or MEK inhibitors in BRAF mutant cancers. Oncotarget 2011, 2 (4), 336-346.
81. Lemech, C.; Infante, J.; Arkenau, H. T. The potential for BRAF V600 inhibitors in advanced cutaneous melanoma: rationale and latest evidence. Ther. Adv. Med. Oncol. 2012, 4 (2), 61-73.
82. Tap, W. D.; Gong, K. W.; Dering, J.; Tseng, Y.; Ginther, C.; Pauletti, G.; Glaspy, J. A.; Essner, R.; Bollag, G.; Hirth, P.; Zhang, C.; Slamon, D. J. Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma. Neoplasia. 2010, 12 (8), 637-649.
83. Shi, H.; Kong, X.; Ribas, A.; Lo, R. S. Combinatorial treatments that overcome PDGFRbeta-driven resistance of melanoma cells to V600EB-RAF inhibition. Cancer Res. 2011, 71 (15), 5067-5074.
84. Shao, Y.; Aplin, A. E. BH3-only protein silencing contributes to acquired resistance to PLX4720 in human melanoma. Cell Death Differ. 2012, 19 (12), 2029-2039.
85. Basile, K. J.; Abel, E. V.; Aplin, A. E. Adaptive upregulation of FOXD3 and resistance to PLX4032/4720-induced cell death in mutant B-RAF melanoma cells. Oncogene. 2012, 31 (19), 2471-2479.
86. Paraiso, K. H.; Haarberg, H. E.; Wood, E.; Rebecca, V. W.; Chen, Y. A.; Xiang, Y.; Ribas, A.; Lo, R. S.; Weber, J. S.; Sondak, V. K.; John, J. K.; Sarnaik, A. A.; Koomen, J. M.; Smalley, K. S. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin. Cancer. Res. 2012, 18 (9), 2502-2514.
87. Das Thakur, M.; Salangsang, F.; Landman, A. S.; Sellers, W. R.; Pryer, N. K.; Levesque, M. P.; Dummer, R.; McMahon, M.; Stuart, D. D. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 2013, 494 (7436), 251-255.
88. Seghers, A. C.; Wilgenhof, S.; Lebbe, C.; Neyns, B. Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor. Melanoma. Res. 2012, 22 (6), 466-472.
89. Haq, R.; Shoag, J.; Andreu-Perez, P.; Yokoyama, S.; Edelman, H.; Rowe, G. C.; Frederick, D. T.; Hurley, A. D.; Nellore, A.; Kung, A. L.; Wargo, J. A.; Song, J. S.; Fisher, D. E.; Arany, Z.; Widlund, H. R. Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF. Cancer Cell 2013, 23 (3), 302-315.
90. Vazquez, F.; Lim, J. H.; Chim, H.; Bhalla, K.; Girnun, G.; Pierce, K.; Clish, C. B.; Granter, S. R.; Widlund, H. R.; Spiegelman, B. M.; Puigserver, P. PGC1alpha expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer Cell 2013, 23 (3), 287-301.
91. Nissan, M. H.; Solit, D. B. The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both? Curr. Oncol. Rep. 2011, 13 (6), 479-487.
92. Wolchok, J. D.; Weber, J. S.; Maio, M.; Neyns, B.; Harmankaya, K.; Chin, K.; Cykowski, L.; de Pril, V.; Humphrey, R.; Lebbe, C. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann. Oncol. 2013., 24(8), 2174-2180.