• Jennifer Divine
  • Anna S. Clayton


Melanoma most commonly presents as a new or changing pigmented lesion on sun exposed skin. The skin cancer can be categorized into varying subtypes based on its clinical appearance and anatomical location. The prognosis is similar amongst the subtypes with tumor thickness as the most important factor for survival. Melanoma staging depends upon the patient’s symptoms, clinical exam and clinician’s index of suspicion. Surgery is the first line treatment for localized melanoma. Advances in tumor genetics and immunology have led to the development of targeted therapies for metastatic disease.


Invasive Melanoma Nevi Genetic mutations BRAF MAPK MEK NRAS Kit CDKN2A Risk factors UV radiation Dysplastic nevi ABCD Dermoscopy Melanoma in situ Nodular melanoma Metastatic melanoma Histology Immunohistochemistry Breslow depth Staging TNM Prognosis Survival Sentinel lymph node Wide local excision Margins Radiation therapy Chemotherapy Adjuvant therapy Immunotherapy Cytokines Cancer vaccine Oncolytic viral therapy Targeted therapy 


  1. 1.
    Erdei E, Torres SM. A new understanding in the epidemiology of melanoma. Expert Rev Anticancer Ther. 2010;10(11):1811–23. Scholar
  2. 2.
    Bradford PT, Anderson WF, Purdue MP, Goldstein AM, Tucker MA. Rising melanoma incidence rates of the trunk among younger women in the United States. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2010;19(9):2401–6. Scholar
  3. 3.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. Scholar
  4. 4.
    Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, Wiggins CL, Wingo PA. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol. 2011;65(5 Suppl 1):S17-25.e11–3. Scholar
  5. 5.
    Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–47. Scholar
  6. 6.
    Millington GW. Mutations of the BRAF gene in human cancer, by Davies et al. (Nature 2002; 417: 949-54). Clin Exp Dermatol. 2013;38(2):222–3. Scholar
  7. 7.
    Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66(20):9818–28. Scholar
  8. 8.
    Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24(26):4340–6. Scholar
  9. 9.
    Bello DM, Ariyan CE, Carvajal RD. Melanoma mutagenesis and aberrant cell signaling. Cancer Control. 2013;20(4):261–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Parkin DM, Mesher D, Sasieni P. 13. Cancers attributable to solar (ultraviolet) radiation exposure in the UK in 2010. Br J Cancer. 2011;105(Suppl 2):S66–9. Scholar
  11. 11.
    Pfahlberg A, Kolmel KF, Gefeller O, Febim Study G. Timing of excessive ultraviolet radiation and melanoma: epidemiology does not support the existence of a critical period of high susceptibility to solar ultraviolet radiation- induced melanoma. Br J Dermatol. 2001;144(3):471–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Green AC, Williams GM, Logan V, Strutton GM. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29(3):257–63. Scholar
  13. 13.
    Ghivasand R, Ruegg CS, Welderpass E, Green AC, Lund E, Velerod MB. Indoor tanning and melanoma risk: long-term evidence from a Prospective Population Based Cohort Study. Am J Epidemol. 2017;185(3):147–56.Google Scholar
  14. 14.
    Friedman RJ, Farber MJ, Warycha MA, Papathasis N, Miller MK, Heilman ER. The "dysplastic" nevus. Clin Dermatol. 2009;27(1):103–15. Scholar
  15. 15.
    Silva JH, Sa BC, Avila AL, Landman G, Duprat Neto JP. Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma – review article. Clinics (Sao Paulo). 2011;66(3):493–9.CrossRefGoogle Scholar
  16. 16.
    Nestle FO, Burg G, Dummer R. New perspectives on immunobiology and immunotherapy of melanoma. Immunol Today. 1999;20(1):5–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Zhang M, Graor H, Yan L, Kim J. Identification of melanoma-reactive CD4+ T-cell subsets from human melanoma draining lymph nodes. J Immunother. 2016;39(1):15–26. Scholar
  18. 18.
    Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant melanoma: the role of physician examination and self-examination of the skin. CA Cancer J Clin. 1985;35:130–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Abbasi NR, Shaw HM, Rigel DS, Friedman RJ, McCarthy WH, Osman I, Kopf AW, Polsky D. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA. 2004;29(22):2771–6.CrossRefGoogle Scholar
  20. 20.
    Grob JJ, Bonerandi JJ. The ‘ugly duckling’ sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol. 1998;134(1):103–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Mar V, Roberts H, Wolfe R, English DR, Kelly JW. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol. 2013;68(4):568–75. Scholar
  22. 22.
    Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, Flaherty KT, Gimotty PA, Johnson T, Johnson MM, Leong SP, Ross MI, Byrd DR, Cascinelli N, Cochran AJ, Eggermont AM, McMasters KM, Mihm MC Jr, Morton DL, Sondak VK. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American joint committee on cancer melanoma staging database. J Clin Oncol. 2011;29(16):2199–205. Scholar
  23. 23.
    Jen M, Murphy M, Grant-Kels JM. Childhood melanoma. Clin Dermatol. 2009;27(6):529–36. Scholar
  24. 24.
    Vestergaard ME, Macaskill P, Holt PE, Menzies SW. Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting. Br J Dermatol. 2008;159(3):669–76. Scholar
  25. 25.
    Gallegos-Hernandez JF, Ortiz-Maldonado AL, Minauro-Munoz GG, Arias-Ceballos H, Hernandez-Sanjuan M. Dermoscopy in cutaneous melanoma. Cir Cir. 2015;83(2):107–11. Scholar
  26. 26.
    Menzies SW, Moloney FJ, Byth K, Avramidis M, Argenziano G, Zalaudek I, Braun RP, Malvehy J, Puig S, Rabinovitz HS, Oliviero M, Cabo H, Bono R, Pizzichetta MA, Claeson M, Gaffney DC, Soyer HP, Stanganelli I, Scolyer RA, Guitera P, Kelly J, McCurdy O, Llambrich A, Marghoob AA, Zaballos P, Kirchesch HM, Piccolo D, Bowling J, Thomas L, Terstappen K, Tanaka M, Pellacani G, Pagnanelli G, Ghigliotti G, Ortega BC, Crafter G, Ortiz AM, Tromme I, Karaarslan IK, Ozdemir F, Tam A, Landi C, Norton P, Kacar N, Rudnicka L, Slowinska M, Simionescu O, Di Stefani A, Coates E, Kreusch J. Dermoscopic evaluation of nodular melanoma. JAMA Dermatol. 2013;149(6):699–709. Scholar
  27. 27.
    Bichakjian CK, Halpern AC, Johnson TM, Foote Hood A, Grichnik JM, Swetter SM, Tsao H, Barbosa VH, Chuang TY, Duvic M, Ho VC, Sober AJ, Beutner KR, Bhushan R, Smith Begolka W, American Academy of Dermatology. Guidelines of care for the management of primary cutaneous melanoma. American Academy of Dermatology. J Am Acad Dermatol. 2011;65(5):1032–47. Scholar
  28. 28.
    Hendi A, Brodland DG, Zitelli JA. Melanocytes in long-standing sun-exposed skin: quantitative analysis using the MART-1 immunostain. Arch Dermatol. 2006;142(7):871–6. Scholar
  29. 29.
    Duffy K, Grossman D. The dysplastic nevus: from historical perspective to management in the modern era: part I. Historical, histologic, and clinical aspects. J Am Acad Dermatol. 2012;67(1):1.e1–16. quiz 17–8. Scholar
  30. 30.
    Patrawala S, Maley A, Greskovich C, Stuart L, Parker D, Swerlick R, Stoff B. Discordance of histopathologic parameters in cutaneous melanoma: clinical implications. J Am Acad Dermatol. 2016;74(1):75–80. Scholar
  31. 31.
    Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, Urist M, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA, Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622–34. Scholar
  32. 32.
    Smoller BR. Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 2006;19(Suppl 2):S34–40. Scholar
  33. 33.
    Schmitt FC, Bacchi CE. S-100 protein: is it useful as a tumour marker in diagnostic immunocytochemistry? Histopathology. 1989;15(3):281–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Gown AM, Vogel AM, Hoak D, Gough F, McNutt MA. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol. 1986;123(2):195–203.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Ohsie SJ, Sarantopoulos GP, Cochran AJ, Binder SW. Immunohistochemical characteristics of melanoma. J Cutan Pathol. 2008;35(5):433–44. Scholar
  36. 36.
    Moretti S, Spallanzani A, Chiarugi A, Fabiani M, Pinzi C. Correlation of Ki-67 expression in cutaneous primary melanoma with prognosis in a prospective study: different correlation according to thickness. J Am Acad Dermatol. 2001;44(2):188–92. Scholar
  37. 37.
    Gershenwald JE, Scolyr RA, Hess KR, et al. Melanoma of the skin. In: Amin MD, editor. AJCC cancer staging manual. 8th ed. Chicago: American Joint Committee on Cancer; 2017. p. 563.CrossRefGoogle Scholar
  38. 38.
    Maurichi A, Miceli R, Camerini T, et al. Prediction of survival in patients with thin melanoma: results from a multi-institution study. J Clin Oncol. 2014;32:2479.CrossRefPubMedGoogle Scholar
  39. 39.
    Schuchter L, Schultz DJ, Synnestvedt M, Trock BJ, Guerry D, Elder DE, Elenitsas R, Clark WH, Halpern AC. A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group. Ann Intern Med. 1996;125(5):369–75.CrossRefPubMedGoogle Scholar
  40. 40.
    Wang TS, Johnson TM, Cascade PN, Redman BG, Sondak VK, Schwartz JL. Evaluation of staging chest radiographs and serum lactate dehydrogenase for localized melanoma. J Am Acad Dermatol. 2004;51(3):399–405. Scholar
  41. 41.
    Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Puleo CA, Coventry BJ, Kashani-Sabet M, Smithers BM, Paul E, Kraybill WG, McKinnon JG, Wang HJ, Elashoff R, Faries MB, MSLT Group. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014; 370(7):599–609. Scholar
  42. 42.
    Biddle DA, Evans HL, Kemp BL, El-Naggar AK, Harvell JD, White WL, Iskandar SS, Prieto VG. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol. 2003;27(5):673–81.CrossRefPubMedGoogle Scholar
  43. 43.
    Carson KF, Wen DR, Li PX, Lana AM, Bailly C, Morton DL, Cochran AJ. Nodal nevi and cutaneous melanomas. Am J Surg Pathol. 1996;20(7):834–40.CrossRefPubMedGoogle Scholar
  44. 44.
    Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Glass EC, Wang HJ, MSLT Group. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355(13):1307–1317. Scholar
  45. 45.
    Wong SL, Morton DL, Thompson JF, Gershenwald JE, Leong SP, Reintgen DS, Gutman H, Sabel MS, Carlson GW, McMasters KM, Tyler DS, Goydos JS, Eggermont AM, Nieweg OE, Cosimi AB, Riker AI, GC D. Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study. Ann Surg Oncol. 2006;13(6):809–16. Scholar
  46. 46.
    Kingham TP, Panageas KS, Ariyan CE, Busam KJ, Brady MS, Coit DG. Outcome of patients with a positive sentinel lymph node who do not undergo completion lymphadenectomy. Ann Surg Oncol. 2010;17(2):514–20. Scholar
  47. 47.
    Faries MB, Thompson JF, Andtbacka RH, Mozzillo N, et al. Complete dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Torjesen I. Sentinel node biopsy for melanoma: unnecessary treatment? BMJ. 2013;346:e8645. Scholar
  49. 49.
    Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206. Scholar
  50. 50.
    Schild SE. Role of radiation therapy in the treatment of melanoma. Expert Rev Anticancer Ther. 2009;9(5):583–6. Scholar
  51. 51.
    Samlowski WE, Watson GA, Wang M, Rao G, Klimo P Jr, Boucher K, Shrieve DC, Jensen RL. Multimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS). Cancer. 2007;109(9):1855–62. Scholar
  52. 52.
    Fuhrmann D, Lippold A, Borrosch F, Ellwanger U, Garbe C, Suter L. Should adjuvant radiotherapy be recommended following resection of regional lymph node metastases of malignant melanomas? Br J Dermatol. 2001;144(1):66–70.CrossRefPubMedGoogle Scholar
  53. 53.
    Yang AS, Chapman PB. The history and future of chemotherapy for melanoma. Hematol Oncol Clin North Am. 2009;23(3):583–597, x. Scholar
  54. 54.
    Kroon HM. Treatment of locally advanced melanoma by isolated limb infusion with cytotoxic drugs. J Skin Cancer. 2011;2011:106573. Scholar
  55. 55.
    Zloza A, Dharmadhikari ND, Huelsmann EJ, Broucek JR, Hughes T, Kohlhapp FJ, Kaufman HL. Low-dose interleukin-2 impairs host anti-tumor immunity and inhibits therapeutic responses in a mouse model of melanoma. Cancer Immunol Immunother. 2017;66(1):9–16. Scholar
  56. 56.
    Schwartz RN, Stover L, Dutcher J. Managing toxicities of high-dose interleukin-2. Oncology (Williston Park). 2002;16(11 Suppl 13):11–20.Google Scholar
  57. 57.
    Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev. 2003;29(4):241–52.CrossRefPubMedGoogle Scholar
  58. 58.
    Ferrantini M, Capone I, Belardelli F. Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie. 2007;89(6–7):884–93. Scholar
  59. 59.
    Sabel MS, Sondak VK. Pros and cons of adjuvant interferon in the treatment of melanoma. Oncologist. 2003;8(5):451–8.CrossRefPubMedGoogle Scholar
  60. 60.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. Scholar
  61. 61.
    Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled analysis of long-term survival data from phase II and phase III trials of Ipilimumab in Unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–94. Scholar
  62. 62.
    Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26. Scholar
  63. 63.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. Scholar
  64. 64.
    Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, Gangadhar TC, Hersey P, Dronca R, Joseph RW, Zarour H, Chmielowski B, Lawrence DP, Algazi A, Rizvi NA, Hoffner B, Mateus C, Gergich K, Lindia JA, Giannotti M, Li XN, Ebbinghaus S, Kang SP, Robert C. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315(15):1600–9. Scholar
  65. 65.
    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 Investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32. Scholar
  66. 66.
    Larkin J, Lao CD, Urba WJ, McDermott DF, Horak C, Jiang J, Wolchok JD. Efficacy and safety of nivolumab in patients with BRAF V600 mutant and BRAF wild-type advanced melanoma: a pooled analysis of 4 clinical trials. JAMA Oncol. 2015;1(4):433–40. Scholar
  67. 67.
    Linardou H, Gogas H. Toxicity management of immunotherapy for patients with metastatic melanoma. Ann Transl Med. 2016;4(14):272. Scholar
  68. 68.
    Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–8. Scholar
  69. 69.
    Kirkwood JM, Lee S, Moschos SJ, Albertini MR, Michalak JC, Sander C, Whiteside T, Butterfield LH, Weiner L. Immunogenicity and antitumor effects of vaccination with peptide vaccine+/−granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696. Clin Cancer Res. 2009;15(4):1443–51. Scholar
  70. 70.
    Chapman PB, Hauschild A, Robert C, Haanen JB, 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 SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. Scholar
  71. 71.
    Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martin-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65. Scholar
  72. 72.
    Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion-Sileni V, Lebbe C, Mandala M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Swann S, Legos JJ, Jin F, Mookerjee B, Flaherty K. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444–51. Scholar
  73. 73.
    Larkin J, Ascierto PA, Dreno B, Atkinson V, Liszkay G, Maio M, Mandala M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867–76. Scholar
  74. 74.
    Daud A, Gill J, Kamra S, Chen L, Ahuja A. Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients. J Hematol Oncol. 2017;10(1):3. Scholar
  75. 75.
    Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;305(22):2327–34. Scholar
  76. 76.
    Meier F, Busch S, Lasithiotakis K, Kulms D, Garbe C, Maczey E, Herlyn M, Schittek B. Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment. Br J Dermatol. 2007;156(6):1204–13. Scholar
  77. 77.
    Lasithiotakis KG, Sinnberg TW, Schittek B, Flaherty KT, Kulms D, Maczey E, Garbe C, Meier FE. Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells. J Invest Dermatol. 2008;128(8):2013–23. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jennifer Divine
    • 1
  • Anna S. Clayton
    • 2
  1. 1.Divine Dermatology and Surgical InstituteFort CollinsUSA
  2. 2.DermatologyVanderbilt University of MedicineNashvilleUSA

Personalised recommendations