Recent Advances in Systemic Therapy for Malignant Melanoma
Main Article Content
Keywords
Immunotherapy, Malignant Melanoma, Biomarkers, Chemotherapy
Abstract
Malignant melanoma is a major contributor of skin cancer related mortality with increasing incidence and resistance to therapy. Advanced melanoma has a poor prognosis with a median overall survival of 8-10 months and a 5-year survival rate of 10%. A better understanding of melanogenesis and the tumor microenvironment has led to the development of several new therapies for metastatic melanoma. This review will provide a comprehensive overview of FDA approved novel systemic therapies for advanced melanoma and of other classes of molecules under clinical investigation. This paper will then look at the key signaling pathways these therapies target and briefly discuss the utility of biomarkers in guiding targeted therapy.
References
1 Garbe C, Eigentler TK, Keilholz U, Hauschild A, Kirkwood JM. Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist. 2011;16:5–24
2 I. Melero, S. Hervas-Stubbs, M. Glennie, D.M. Pardoll, L. Chen, Immunostimulatory monoclonal antibodies for cancer therapy, Nat. Rev. Cancer 7 (2007) 95–106
3 T. Nomura, K. Kabashima, Y. Miyachi, The panoply of abT cells in the skin, J. Dermatol. Sci. 76 (2014)
4 Harlin H, Kuna TV, Peterson AC, Meng Y, Gajewski TF. Tumor progression despite massive influx of activated CD8(+) T cells in a patient with malignant melanoma ascites. Cancer Immunol Immunother. 2006;55:1185–97.
5 S.A. Rosenberg, M.E. Dudley, Adoptive cell therapy for the treatment of patients with metastatic melanoma, Curr. Opin. Immunol. 21 (2009) 233–240
6 Akiyama Y, Nonomura C, Kondou R, Miyata H, Ashizawa T, Maeda C, Mitsuya K, Hayashi N, Nakasu Y, Yamaguchi K. Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells. Int J Oncol. 2016;49:1099–1107. doi: 10.3892/ijo.2016.3586
7 Zhang Y, Song Y, Gao Q. Increased survival time of a patient with metastatic malignant melanoma following immunotherapy: A case report and literature review. Oncol Lett. 2015;10:883–886. doi: 10.3892/ol.2015.3296.
8 Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol. 2018;52(4):1071–1080. doi:10.3892/ijo.2018.4287
9 F.S. Hodi, M. Butler, D.A. Oble, M.V. Seiden, F.G. Haluska, A. Kruse, et al., Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients, Proc Natl Acad Sci US A 105 (2008) 3005–3010.
10 L.S. Walker, D.M. Sansom, The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses, Nat. Rev. Immunol. 11 (2011) 852–863. [7] D. Schadendorf, F.S. Hodi, C. Robert, J.S. Weber, K. Margolin, O. Hamid, et al., Pooled analysis of long-Term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma, J. Clin. Oncol. 33 (2015) 1889–1894
11 D. Schadendorf, F.S. Hodi, C. Robert, J.S. Weber, K. Margolin, O. Hamid, et al., Pooled analysis of long-Term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma, J. Clin. Oncol. 33 (2015) 1889–1894.
12 Weide B, Martens A, Wistuba-Hamprecht K, et al. Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma—safety and efficacy in a phase II study. Cancer Immunol Immunother. 2017;66(4):441–449.
13 R.V. Parry, J.M. Chemnitz, K.A. Frauwirth, A.R. Lanfranco, I. Braunstein, S.V. Kobayashi, et al., CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms, Mol. Cell. Biol. 25 (2005) 9543–9553
14 S.L. Topalian, F.S. Hodi, J.R. Brahmer, S.N. Gettinger, D.C. Smith, D.F. McDermott, et al., Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med. 366 (2012) 2443–2454.
15 J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.J. Grob, C.L. Cowey, C.D. Lao, et al., Combined nivolumab and ipilimumab or monotherapy in untreated melanoma, N. Engl. J. Med. 373 (2015) 23–34.
16 Panelli MC, Wunderlich J, Jeffries J, et al. Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother. 2000;23(4):487–498.
17 Yuan J, Ku GY, Gallardo HF, et al. Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma. Cancer Immun. 2009;9(1):5.
18 Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D. Immunotherapy in melanoma: recent advances and future directions. Eur J Surg Oncol. 2017;43(3):604–611.
19 Pol J, Kroemer G, Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology. 2015;5(1):e1115641.
20 Hersey P, Gallagher S. Intralesional immunotherapy for melanoma. J Surg Oncol. 2014;109(4):320–326.
21 D.A. Schaer, D. Hirschhorn-Cymerman, J.D. Wolchok, Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy, J Immunother Cancer 2 (2014)
22 Dudley ME, Yang JC, Sherry R, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–5239.
23 S.A. Rosenberg, M.E. Dudley, Adoptive cell therapy for the treatment of patients with metastatic melanoma, Curr. Opin. Immunol. 21 (2009) 233–240
24 Y. Kawakami, T. Yaguchi, H. Sumimoto, C. Kudo-Saito, N. Tsukamoto, T. IwataKajihara, et al., Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy, Ann. N. Y. Acad. Sci. 1284 (2013) 80– 86
25 Livingstone E, Zimmer L, Vaubel J, Schadendorf D. BRAF, MEK and KIT inhibitors for melanoma: adverse events and their management. Chin Clin Oncol. 2014;3(3):29.
26 Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516.
27 Wright CJ, McCormack PL. Trametinib: first global approval. Drugs. 2013;73(11):1245–1254.
28 Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–114.
29 Niezgoda A, Niezgoda P, Czajkowski R. Novel approaches to treatment of advanced melanoma: a review on targeted therapy and immunotherapy. Biomed Res Int. 2015;2015:851387.
30 Carlino MS, Todd JR, Rizos H. Resistance to c-kit inhibitors in melanoma: insights for future therapies. Oncoscience. 2014;1(6):423–426.
31Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013;31(26):3182–3190
32 Hodi FS, Friedlander P, Corless CL, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol. 2008;26(12):2046–2051
33 Guo J, Si L, Kong Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011;29(21):2904–2909
34 Pópulo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci. 2012;13(2):1886–1918.
35 Li X, Wu D, Shen J, Zhou M, Lu Y. Rapamycin induces autophagy in the melanoma cell line M14 via regulation of the expression levels of Bcl-2 and Bax. Oncol Lett. 2013;5(1):167–172.
36 Populo H, Soares P, Faustino A, et al. mTOR pathway activation in cutaneous melanoma is associated with poorer prognosis characteristics. Pigment Cell Melanoma Res. 2011;24(1):254–257.
37 Klein A, Sagi-Assif O, Meshel T, et al. CCR4 is a determinant of melanoma brain metastasis.
Oncotarget. 2017;8(19):31079–31091. doi:10.18632/oncotarget.16076
38 D. Sugiyama, H. Nishikawa, Y. Maeda, M. Nishioka, A. Tanemura, I. Katayama, et al., Anti-CCR4 mAb selectively depletes effector-type FoxP3 + CD4+ regulatory Tcells, evoking antitumor immune responses in humans, Proc. Natl. Acad. Sci. U.S.A. 110 (2013) 17945–17950
39 Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol. 2018;52(4):1071–1080. doi:10.3892/ijo.2018.4287
40Velho, Tiago Rodrigues. “Metastatic melanoma - a review of current and future drugs.” Drugs in context vol. 2012 212242. 19 Nov. 2012, doi:10.7573/dic.212242
41 Lui P, Cashin R, Machado M, Hemels M, Corey-Lisle PK, Einarson TR. Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treat Rev. 2007;33(8):665–80.
42 Serrone L, Zeuli M, Sega FM, Cognetti F. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res. 2000;19(1):21–34.
43 S. Gebremeskel, B. Johnston, Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies, Oncotarget 6 (2015) 41600–41619.
44 Soliman HH, Minton SE, Han HS, et al. A phase I study of indoximod in patients with advanced malignancies. Oncotarget. 2016;7:22928.
45 Davies H, Bignell GR, Cox C, Stephens P. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949.
46 Tas F, Duranyildiz D, Oguz H, Camlica H, Yasasever V, Topuz E. Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients. Melanoma Res. 2006;16(5):405–411.
47 Mehnert JM, McCarthy MM, Jilaveanu L, et al. Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays. Hum Pathol. 2010;41(3):375–384.
48 Von Moos R, Seifert B, Simcock M, et al. First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07) Ann Oncol. 2011;23(2):531–536.
49 McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Bäsecke J, et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 2011;226:2762–2781. doi: 10.1002/jcp.22647.
50 Steelman LS, Chappell WH, Abrams SL, Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY) 2011;3:192–222. doi: 10.18632/aging.100296.
51 McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: How mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 2012;3:1068–1111. doi: 10.18632/oncotarget.659.
52 Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330. doi: 10.1056/NEJMoa1412082.
53 Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–39. doi: 10.1056/NEJMoa1412690.
54 Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD 1 blockade in melanoma. N Engl J Med. 2016;375:819–829. doi: 10.1056/NEJMoa1604958.
55 M.S. Lawrence, P. Stojanov, P. Polak, G.V. Kryukov, K. Cibulskis, A. Sivachenko, et al., Mutational heterogeneity in cancer and the search for new cancerassociated genes, Nature 499 (2013) 214–218.
56 W. Hugo, J.M. Zaretsky, L. Sun, C. Song, B.H. Moreno, S. Hu-Lieskovan, et al., Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma, Cell 165 (2016) 35–44.
57 N. McGranahan, A.J. Furness, R. Rosenthal, S. Ramskov, R. Lyngaa, S.K. Saini, et al., Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade, Science 351 (2016) 1463–1469.
58 Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.
59 Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N Engl J Med, 2012, vol. 366 (pg. 2443-54)
60 Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma, N Engl J Med, 2013, vol. 369 (pg. 122-33)
61 Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation, N Engl J Med, 2011, vol.364 (2507-16)
62 Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma, N Engl J Med, 2012, vol. 367 (pg. 107-14)
63 Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations, N Engl J Med, 2012, vol. 367 (pg. 1694-703)
2 I. Melero, S. Hervas-Stubbs, M. Glennie, D.M. Pardoll, L. Chen, Immunostimulatory monoclonal antibodies for cancer therapy, Nat. Rev. Cancer 7 (2007) 95–106
3 T. Nomura, K. Kabashima, Y. Miyachi, The panoply of abT cells in the skin, J. Dermatol. Sci. 76 (2014)
4 Harlin H, Kuna TV, Peterson AC, Meng Y, Gajewski TF. Tumor progression despite massive influx of activated CD8(+) T cells in a patient with malignant melanoma ascites. Cancer Immunol Immunother. 2006;55:1185–97.
5 S.A. Rosenberg, M.E. Dudley, Adoptive cell therapy for the treatment of patients with metastatic melanoma, Curr. Opin. Immunol. 21 (2009) 233–240
6 Akiyama Y, Nonomura C, Kondou R, Miyata H, Ashizawa T, Maeda C, Mitsuya K, Hayashi N, Nakasu Y, Yamaguchi K. Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells. Int J Oncol. 2016;49:1099–1107. doi: 10.3892/ijo.2016.3586
7 Zhang Y, Song Y, Gao Q. Increased survival time of a patient with metastatic malignant melanoma following immunotherapy: A case report and literature review. Oncol Lett. 2015;10:883–886. doi: 10.3892/ol.2015.3296.
8 Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol. 2018;52(4):1071–1080. doi:10.3892/ijo.2018.4287
9 F.S. Hodi, M. Butler, D.A. Oble, M.V. Seiden, F.G. Haluska, A. Kruse, et al., Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients, Proc Natl Acad Sci US A 105 (2008) 3005–3010.
10 L.S. Walker, D.M. Sansom, The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses, Nat. Rev. Immunol. 11 (2011) 852–863. [7] D. Schadendorf, F.S. Hodi, C. Robert, J.S. Weber, K. Margolin, O. Hamid, et al., Pooled analysis of long-Term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma, J. Clin. Oncol. 33 (2015) 1889–1894
11 D. Schadendorf, F.S. Hodi, C. Robert, J.S. Weber, K. Margolin, O. Hamid, et al., Pooled analysis of long-Term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma, J. Clin. Oncol. 33 (2015) 1889–1894.
12 Weide B, Martens A, Wistuba-Hamprecht K, et al. Combined treatment with ipilimumab and intratumoral interleukin-2 in pretreated patients with stage IV melanoma—safety and efficacy in a phase II study. Cancer Immunol Immunother. 2017;66(4):441–449.
13 R.V. Parry, J.M. Chemnitz, K.A. Frauwirth, A.R. Lanfranco, I. Braunstein, S.V. Kobayashi, et al., CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms, Mol. Cell. Biol. 25 (2005) 9543–9553
14 S.L. Topalian, F.S. Hodi, J.R. Brahmer, S.N. Gettinger, D.C. Smith, D.F. McDermott, et al., Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med. 366 (2012) 2443–2454.
15 J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.J. Grob, C.L. Cowey, C.D. Lao, et al., Combined nivolumab and ipilimumab or monotherapy in untreated melanoma, N. Engl. J. Med. 373 (2015) 23–34.
16 Panelli MC, Wunderlich J, Jeffries J, et al. Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother. 2000;23(4):487–498.
17 Yuan J, Ku GY, Gallardo HF, et al. Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma. Cancer Immun. 2009;9(1):5.
18 Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D. Immunotherapy in melanoma: recent advances and future directions. Eur J Surg Oncol. 2017;43(3):604–611.
19 Pol J, Kroemer G, Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology. 2015;5(1):e1115641.
20 Hersey P, Gallagher S. Intralesional immunotherapy for melanoma. J Surg Oncol. 2014;109(4):320–326.
21 D.A. Schaer, D. Hirschhorn-Cymerman, J.D. Wolchok, Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy, J Immunother Cancer 2 (2014)
22 Dudley ME, Yang JC, Sherry R, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–5239.
23 S.A. Rosenberg, M.E. Dudley, Adoptive cell therapy for the treatment of patients with metastatic melanoma, Curr. Opin. Immunol. 21 (2009) 233–240
24 Y. Kawakami, T. Yaguchi, H. Sumimoto, C. Kudo-Saito, N. Tsukamoto, T. IwataKajihara, et al., Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy, Ann. N. Y. Acad. Sci. 1284 (2013) 80– 86
25 Livingstone E, Zimmer L, Vaubel J, Schadendorf D. BRAF, MEK and KIT inhibitors for melanoma: adverse events and their management. Chin Clin Oncol. 2014;3(3):29.
26 Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516.
27 Wright CJ, McCormack PL. Trametinib: first global approval. Drugs. 2013;73(11):1245–1254.
28 Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–114.
29 Niezgoda A, Niezgoda P, Czajkowski R. Novel approaches to treatment of advanced melanoma: a review on targeted therapy and immunotherapy. Biomed Res Int. 2015;2015:851387.
30 Carlino MS, Todd JR, Rizos H. Resistance to c-kit inhibitors in melanoma: insights for future therapies. Oncoscience. 2014;1(6):423–426.
31Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013;31(26):3182–3190
32 Hodi FS, Friedlander P, Corless CL, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol. 2008;26(12):2046–2051
33 Guo J, Si L, Kong Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol. 2011;29(21):2904–2909
34 Pópulo H, Lopes JM, Soares P. The mTOR signalling pathway in human cancer. Int J Mol Sci. 2012;13(2):1886–1918.
35 Li X, Wu D, Shen J, Zhou M, Lu Y. Rapamycin induces autophagy in the melanoma cell line M14 via regulation of the expression levels of Bcl-2 and Bax. Oncol Lett. 2013;5(1):167–172.
36 Populo H, Soares P, Faustino A, et al. mTOR pathway activation in cutaneous melanoma is associated with poorer prognosis characteristics. Pigment Cell Melanoma Res. 2011;24(1):254–257.
37 Klein A, Sagi-Assif O, Meshel T, et al. CCR4 is a determinant of melanoma brain metastasis.
Oncotarget. 2017;8(19):31079–31091. doi:10.18632/oncotarget.16076
38 D. Sugiyama, H. Nishikawa, Y. Maeda, M. Nishioka, A. Tanemura, I. Katayama, et al., Anti-CCR4 mAb selectively depletes effector-type FoxP3 + CD4+ regulatory Tcells, evoking antitumor immune responses in humans, Proc. Natl. Acad. Sci. U.S.A. 110 (2013) 17945–17950
39 Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol. 2018;52(4):1071–1080. doi:10.3892/ijo.2018.4287
40Velho, Tiago Rodrigues. “Metastatic melanoma - a review of current and future drugs.” Drugs in context vol. 2012 212242. 19 Nov. 2012, doi:10.7573/dic.212242
41 Lui P, Cashin R, Machado M, Hemels M, Corey-Lisle PK, Einarson TR. Treatments for metastatic melanoma: synthesis of evidence from randomized trials. Cancer Treat Rev. 2007;33(8):665–80.
42 Serrone L, Zeuli M, Sega FM, Cognetti F. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res. 2000;19(1):21–34.
43 S. Gebremeskel, B. Johnston, Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: impact on clinical studies and considerations for combined therapies, Oncotarget 6 (2015) 41600–41619.
44 Soliman HH, Minton SE, Han HS, et al. A phase I study of indoximod in patients with advanced malignancies. Oncotarget. 2016;7:22928.
45 Davies H, Bignell GR, Cox C, Stephens P. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949.
46 Tas F, Duranyildiz D, Oguz H, Camlica H, Yasasever V, Topuz E. Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients. Melanoma Res. 2006;16(5):405–411.
47 Mehnert JM, McCarthy MM, Jilaveanu L, et al. Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays. Hum Pathol. 2010;41(3):375–384.
48 Von Moos R, Seifert B, Simcock M, et al. First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07) Ann Oncol. 2011;23(2):531–536.
49 McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Bäsecke J, et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 2011;226:2762–2781. doi: 10.1002/jcp.22647.
50 Steelman LS, Chappell WH, Abrams SL, Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY) 2011;3:192–222. doi: 10.18632/aging.100296.
51 McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: How mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 2012;3:1068–1111. doi: 10.18632/oncotarget.659.
52 Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330. doi: 10.1056/NEJMoa1412082.
53 Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–39. doi: 10.1056/NEJMoa1412690.
54 Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD 1 blockade in melanoma. N Engl J Med. 2016;375:819–829. doi: 10.1056/NEJMoa1604958.
55 M.S. Lawrence, P. Stojanov, P. Polak, G.V. Kryukov, K. Cibulskis, A. Sivachenko, et al., Mutational heterogeneity in cancer and the search for new cancerassociated genes, Nature 499 (2013) 214–218.
56 W. Hugo, J.M. Zaretsky, L. Sun, C. Song, B.H. Moreno, S. Hu-Lieskovan, et al., Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma, Cell 165 (2016) 35–44.
57 N. McGranahan, A.J. Furness, R. Rosenthal, S. Ramskov, R. Lyngaa, S.K. Saini, et al., Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade, Science 351 (2016) 1463–1469.
58 Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.
59 Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N Engl J Med, 2012, vol. 366 (pg. 2443-54)
60 Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma, N Engl J Med, 2013, vol. 369 (pg. 122-33)
61 Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation, N Engl J Med, 2011, vol.364 (2507-16)
62 Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma, N Engl J Med, 2012, vol. 367 (pg. 107-14)
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Published
Jan 28, 2020
Article Details
How to Cite
Khan, U., Kaushik, S., & Anvekar, R. (2020). Recent Advances in Systemic Therapy for Malignant Melanoma. SKIN The Journal of Cutaneous Medicine, 4(1), 4–14. https://doi.org/10.25251/skin.4.1.2
Section
In-Depth Reviews
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Author Biography
Umair Khan, Mount Sinai Health Systems
Melanoma Fellow at the Tisch Cancer Institute
Under the tutelage of Dr. Jerry Chipuk?
?