Resistance to combination BRAF and MEK inhibition in metastatic melanoma: Where to next?

European Journal of Cancer

Volumn 62, Issue , 2016, Pages 76-85

  Welsh, Sarah J ^a,b   Rizos, Helen ^a,b   Scolyer, Richard A ^b,c   Long, Georgina V ^b,c  

^a MACQUARIE UNIVERSITY   (Australia)

^b MELANOMA INSTITUTE AUSTRALIA   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

Author keywords

BRAF inhibition; Immunotherapy; MAPK signalling; MEK inhibition; Melanoma; Resistance

Indexed keywords

B RAF KINASE; B RAF KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE INHIBITOR; ANTINEOPLASTIC AGENT; IMMUNOSUPPRESSIVE AGENT; MONOCLONAL ANTIBODY; PROTEIN KINASE INHIBITOR;

CANCER RESISTANCE; ENZYME INHIBITION; GENE ACTIVATION; GENE MUTATION; HUMAN; IMMUNOMODULATION; METASTATIC MELANOMA; MOLECULARLY TARGETED THERAPY; NONHUMAN; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DRUG RESISTANCE; IMMUNOLOGY; IMMUNOTHERAPY; MELANOMA; PROCEDURES; SECONDARY;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; MAP KINASE SIGNALING SYSTEM; MELANOMA; MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS B-RAF;

EID: 84971231413     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2016.04.005     Document Type: Review

References (72)

1. J. Ferlay, I. Soerjomataram, M. Ervik, R. Dikshit, S. Eser, C. Mathers, and et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet] 2013 International Agency for Research on Cancer Lyon, France Available from: http://globocan.iarc.fr [accessed on 21.03.16]
2. A.M. Menzies, and G.V. Long Systemic treatment for BRAF-mutant melanoma: where do we go next? Lancet Oncol 15 9 2014 Aug e371 e381
3. K.T. Flaherty Dividing and conquering: controlling advanced melanoma by targeting oncogene-defined subsets Clin Exp Metastasis 29 7 2012 841 846
4. A. Ribas, and K.T. Flaherty BRAF targeted therapy changes the treatment paradigm in melanoma Nat Rev Clin Oncol 8 7 2011 May 24 426 433
5. P.B. Chapman, A. Hauschild, C. Robert, J.B. Haanen, P. Ascierto, J. Larkin, et al. BRIM-3 Study Group Improved survival with vemurafenib in melanoma with BRAF V600E mutation N Engl J Med 364 26 2011 Jun 30 2507 2516
6. A. Hauschild, J.J. Grob, L.V. Demidov, T. Jouary, R. Gutzmer, M. Millward, and et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial Lancet 380 9839 2012 Jul 28 358 365
7. G.V. Long, D. Stroyakovskiy, H. Gogas, E. Levchenko, F. de Braud, J. Larkin, and et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma N Engl J Med 371 20 2014, Nov 13 1877 1888
8. G.V. Long, D. Stroyakovskiy, H. Gogas, E. Levchenko, F. de Braud, J. Larkin, and et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial Lancet 386 9992 2015 Aug 1 444 451
9. C. Robert, B. Karaszewska, J. Schachter, P. Rutkowski, A. Mackiewicz, D. Stroiakovski, and et al. Improved overall survival in melanoma with combined dabrafenib and trametinib N Engl J Med 372 1 2015, Jan 1 30 39
10. H. Rizos, A.M. Menzies, G.M. Pupo, M.S. Carlino, C. Fung, J. Hyman, and et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact Clin Cancer Res 20 7 2014 Apr 1 1965 1977
11. H. Shi, W. Hugo, X. Kong, A. Hong, R.C. Koya, G. Moriceau, and et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy Cancer Discov 4 2014 80 93
12. E.M. Van Allen, N. Wagle, A. Sucker, D.J. Treacy, C.M. Johannessen, E.M. Goetz, and et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma Cancer Discov 4 2014 94 109
13. K.T. Flaherty, J.R. Infante, A. Daud, R. Gonzalez, R.F. Kefford, J. Sosman, and et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations N Engl J Med 367 18 2012 Nov 1694 1703
14. G.V. Long, J.S. Weber, J.R. Infante, K.B. Kim, A. Daud, R. Gonzalez, and et al. Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib J Clin Oncol 34 8 2016 Mar 10 871 878
15. F. Su, A. Viros, C. Milagre, K. Trunzer, G. Bollag, O. Spleiss, and et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors N Engl J Med 366 3 2012 Jan 19 207 215
16. J. Larkin, P.A. Ascierto, B. Dréno, V. Atkinson, G. Liszkay, M. Maio, and et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma N Engl J Med 371 20 2014 Nov 13 1867 1876
17. S. Whittaker, R. Kirk, R. Hayward, A. Zambon, A. Viros, N. Cantarino, and et al. Gatekeeper mutations mediate resistance to BRAF-targeted therapies Sci Transl Med 2 35 2010 35ra41
18. I.V. Fedorenko, K.H. Paraiso, and K.S. Smalley Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma Biochem Pharmacol 82 3 2011 201 209
19. P.I. Poulikakos, Y. Persaud, M. Janakiraman, X. Kong, C. Ng, G. Moriceau, and et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E) Nature 480 7377 2011 Nov 23 387 390
20. H. Shi, G. Moriceau, X. Kong, M.K. Lee, H. Lee, R.C. Koya, and et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance Nat Commun 3 2012 Mar 6 724
21. M.S. Carlino, C. Fung, H. Shahheydari, J.R. Todd, S.C. Boyd, M. Irvine, and et al. Preexisting MEK1P124 mutations diminish response to BRAF inhibitors in metastatic melanoma patients Clin Cancer Res 21 1 2015 Jan 1 98 105
22. N. Wagle, E.M. Van Allen, D.J. Treacy, D.T. Frederick, Z.A. Cooper, A. Taylor-Weiner, and et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition Cancer Discov 4 2014 61 68
23. C.M. Johannessen, J.S. Boehm, S.Y. Kim, S.R. Thomas, L. Wardwell, L.A. Johnson, and et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation Nature 468 7326 2010 Dec 16 968 972
24. G.V. Long, C. Fung, A.M. Menzies, G.M. Pupo, M.S. Carlino, J. Hyman, and et al. Rizos H.Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma Nat Commun 5 2014, Dec 2 5694
25. E. Hirata, M.R. Girotti, A. Viros, S. Hooper, B. Spencer-Dene, M. Matsuda, and et al. Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin β1/FAK signaling Cancer Cell 27 4 2015 574 588
26. M.S. Carlino, J.R. Todd, K. Gowrishankar, B. Mijatov, G.M. Pupo, C. Fung, and et al. Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma Mol Oncol 8 3 2014 May 544 554
27. S.R. Whittaker, J.P. Theurillat, E. Van Allen, N. Wagle, J. Hsiao, G.S. Cowley, and et al. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition Cancer Discov 3 3 2013 Mar 350 362
28. G. Moriceau, W. Hugo, A. Hong, H. Shi, X. Kong, C.C. Yu, and et al. Tunable combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/ MEK cotargeting but result in melanoma drug addiction Cancer Cell 27 2015 240 256
29. J. Larkin, Y. Yan, G.A. McArthur, P.A. Ascierto, G. Liszkay, M. Maio, and et al. Update of progression-free survival (PFS) and correlative biomarker analysis from coBRIM: phase III study of cobimetinib (cobi) plus vemurafenib (vem) in advanced BRAF-mutated melanoma J Clin Oncol 33 2015 [suppl; abstr 9006]
30. D.J. Wong, L. Robert, M.S. Atefi, A. Lassen, G. Avarappatt, M. Cerniglia, and et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant NRAS mutant and wild-type melanoma.Mol Cancer 13 2014 Aug 20 194
31. V.W. Rebecca, G.M. Alicea, K.H. Paraiso, H. Lawrence, G.T. Gibney, and K.S. Smalley Vertical inhibition of the MAPK pathway enhances therapeutic responses in NRAS-mutant melanoma Pigment Cell Melanoma Res 27 6 2014 Nov 1154 1158
32. A.D. Bucheit, and M.A. Davies Emerging insights into resistance to BRAF inhibitors in melanoma Biochem Pharmacol 87 3 2014 Feb 1 381 389
33. R. Nazarian, H. Shi, Q. Wang, X. Kong, R.C. Koya, H. Lee, and et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation Nature 468 7326 2010 Dec 16 973 977
34. R. Straussman, T. Morikawa, K. Shee, M. Barzily-Rokni, Z.R. Qian, J. Du, and et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion Nature 487 7408 2012 Jul 26 500 504
35. T.R. Wilson, J. Fridlyand, Y. Yan, E. Penuel, L. Burton, E. Chan, and et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors Nature 487 7408 2012 505 509
36. J. Villanueva, A. Vultur, J.T. Lee, R. Somasundaram, M. Fukunaga-Kalabis, A.K. Cipolla, and et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K Cancer Cell 18 6 2010 Dec 14 683 695
37. A.H. Aguissa-Toure, and G. Li Genetic alterations of PTEN in human melanoma Cell Mol Life Sci 69 2012 1475 1491
38. B. Chen, C. Tardell, B. Higgins, K. Packman, J.F. Boylan, and H. Niu BRAFV600E negatively regulates the AKT pathway in melanoma cell lines PLoS One 7 8 2012 e42598
39. Y.N. Gopal, H. Rizos, G. Chen, W. Deng, D.T. Frederick, Z.A. Cooper, and et al. Inhibition of mTORC1/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1α and oxidative phosphorylation in melanoma Cancer Res 74 23 2014 Dec 1 7037 7047
40. M. Dugo, G. Nicolini, G. Tragni, I. Bersani, A. Tomassetti, V. Colonna, and et al. A melanoma subtype with intrinsic resistance to BRAF inhibition identified by receptor tyrosine kinases gene-driven classification Oncotarget 6 7 2015 Mar 10 5118 5133
41. F. Catalanotti, D.B. Solit, M.P. Pulitzer, M.F. Berger, S.N. Scott, T. Iyriboz, and et al. Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma Clin Cancer Res 19 2013 2257 2264
42. Y.N. Gopal, W. Deng, S.E. Woodman, K. Komurov, P. Ram, P.D. Smith, and et al. Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells Cancer Res 70 2010 8736 8747
43. M. Atefi, E. von Euw, N. Attar, C. Ng, C. Chu, D. Guo, and et al. Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway PLoS One 6 12 2011 e28973
44. M. Sweetlove, E. Wrightson, S. Kolekar, G.W. Rewcastle, B.C. Baguley, P.R. Shepherd, and S.M. Jamieson Inhibitors of pan-PI3K signaling synergize with BRAF or MEK inhibitors to prevent BRAF-mutant melanoma cell growth Front Oncol 5 2015 Jun 16 135
45. N. Komatsu, Y. Fujita, M. Matsuda, and K. Aoki mTORC1 upregulation via ERK-dependent gene expression change confers intrinsic resistance to MEK inhibitors in oncogenic KRas-mutant cancer cells Oncogene 2015 Feb 23
46. A. Roesch Tumor heterogeneity and plasticity as elusive drivers for resistance to MAPK pathway inhibition in melanoma Oncogene 34 2015 2951 2957
47. K. Gowrishankar, S. Snoyman, G.M. Pupo, T.M. Becker, R.F. Kefford, and H. Rizos Acquired resistance to BRAF inhibition can confer cross-resistance to combined BRAF/MEK inhibition J Invest Dermatol 132 2012 1850 1859
48. T.A. Yap, L. Bjerke, P.A. Clarke, and P. Workman Drugging PI3K in cancer: refining targets and therapeutic strategies Curr Opin Pharmacol 23 2015 Aug 98 107
49. K. Margolin, J. Longmate, T. Baratta, T. Synold, S. Christensen, J. Weber, and et al. CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium Cancer 104 2005 1045 1048
50. R.D. Rao, H.E. Windschitl, J.B. Allred, V.J. Lowe, W.J. Maples, M.K. Gornet, and et al. Phase II trial of the mTOR inhibitor everolimus (RAD001) in metastatic melanoma [abstract #8043] J Clin Oncol 24 2006 463s
51. L. Hui, and Y. Chen Tumor microenvironment: sanctuary of the devil Cancer Lett 15 2015 Aug 11 00507 00508 pii: S0304-3835
52. T. Schatton, R.A. Scolyer, J.F. Thompson, and M.C. Mihm Jr. Tumor-infiltrating lymphocytes and their significance in melanoma prognosis Methods Mol Biol 1102 2014 287 324
53. H. Kakavand, J.S. Wilmott, A.M. Menzies, R. Vilain, L.E. Haydu, J.H. Yearley, and et al. PD-L1 expression and tumor-infiltrating lymphocytes define different subsets of MAPK inhibitor-treated melanoma patients Clin Cancer Res 21 14 2015 Jul 15 3140 3148
54. Z.A. Cooper, D.T. Frederick, V.R. Juneja, R.J. Sullivan, D.P. Lawrence, A. Piris, and et al. BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes Oncoimmunology 2 10 2013 Oct 1 e26615
55. J.S. Wilmott, G.V. Long, J.R. Howle, L.E. Haydu, R.N. Sharma, J.F. Thompson, and et al. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma Clin Cancer Res 18 5 2012 Mar 1 1386 1394
56. D.T. Frederick, A. Piris, A.P. Cogdill, Z.A. Cooper, C. Lezcano, C.R. Ferrone, and et al. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma Clin Cancer Res 19 5 2013 1225 1231
57. D. Massi, D. Brusa, B. Merelli, C. Falcone, G. Xue, A. Carobbio, and et al. The status of PD-L1 and tumor-infiltrating immune cells predict resistance and poor prognosis in BRAFi-treated melanoma patients harboring mutant BRAFV600 Ann Oncol 26 9 2015 Sep 1980 1987
58. S. Mok, J. Tsoi, R.C. Koya, S. Hu-Lieskovan, B.L. West, G. Bollag, and et al. Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition BMC Cancer 15 2015 356
59. R.C. Koya, S. Mok, N. Otte, K.J. Blacketor, B. Comin-Anduix, P.C. Tumeh, and et al. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy Canc Res 72 16 2012 3928 3937
60. Cancer Genome Atlas Network Genomic classification of cutaneous melanoma Cell 161 7 2015 Jun 18 1681 1696
61. J. Cohen, and M. Sznol Therapeutic combinations of immune-modulating antibodies in melanoma and beyond Semin Oncol 42 3 2015 Jun 488 494 10.1053/j.seminoncol.2015.02.014 [Epub 2015 Feb 14]
62. F.S. Hodi, S.J. O'Day, D.F. McDermott, R.W. Weber, J.A. Sosman, J.B. Haanen, and et al. Improved survival with ipilimumab in patients with metastatic melanoma N Engl J Med 363 8 2010 Aug 19 711 723 10.1056/NEJMoa1003466 [Epub 2010 Jun 5. Erratum in: N Engl J Med. 2010 Sep 23;363(13):1290]
63. S.L. Topalian, M. Sznol, D.F. McDermott, H.M. Kluger, R.D. Carvajal, W.H. Sharfman, and et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab J Clin Oncol 32 10 2014 Apr 1 1020 1030
64. C. Robert, G.V. Long, B. Brady, C. Dutriaux, M. Maio, L. Mortier, and et al. Nivolumab in previously untreated melanoma without BRAF mutation N Engl J Med 372 4 2015 320 330
65. C. Robert, J. Schachter, G.V. Long, A. Arance, J.J. Grob, L. Mortier, et al. KEYNOTE-006 investigators Pembrolizumab versus ipilimumab in advanced melanoma N Engl J Med 372 26 2015 2521 2532
66. J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.J. Grob, C.L. Cowey, C.D. Lao, and et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma N Engl J Med 373 1 2015 Jul 2 23 34
67. P.C. Tumeh, C.L. Harview, J.H. Yearley, I.P. Shintaku, E.J. Taylor, L. Robert, and et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance Nature 515 7528 2014 Nov 27 568 571
68. R.E. Vilain, H. Kakavand, A.M. Menzies, J. Madore, J. Wilmott, R. Dobney, and et al. PD1 inhibition-induced changes in melanoma and its associated immune infiltrate ESMO presentation 2016 [2015. Abstract 3305. Publication in press]
69. A. Ribas, D.S. Shin, J. Zaretsky, J. Frederiksen, A. Cornish, E. Avramis, and et al. PD-1 blockade expands intratumoral memory T cells Cancer Immunol Res 4 3 2016 Mar 194 203
70. D.B. Johnson, K.T. Flaherty, J.S. Weber, J.R. Infante, K.B. Kim, R.F. Kefford, and et al. Combined BRAF (dabrafenib) and MEK inhibition (trametinib) in patients with BRAFV600-Mutant melanoma experiencing progression with single-agent BRAF inhibitor J Clin Oncol 32 2014 3697 3704
71. S. Hu-Lieskovan, S. Mok, B. Homet Moreno, J. Tsoi, L. Robert, L. Goedert, and et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma Sci Transl Med 7 279 2015 Mar 18 279ra41
72. Z.A. Cooper, V.R. Juneja, P.T. Sage, D.T. Frederick, A. Piris, D. Mitra, and et al. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade Cancer Immunol Res 2 7 2014 Jul 643 654