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American Journal of Clinical Dermatology
Erschienen in: American Journal of Clinical Dermatology 3/2017

01.06.2017 | Current Opinion

Next-Generation Sequencing to Guide Treatment of Advanced Melanoma

verfasst von: Klaus G. Griewank, Bastian Schilling

Erschienen in: American Journal of Clinical Dermatology | Ausgabe 3/2017

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Abstract

Next-generation sequencing (NGS) has provided significant insights into the pathogenesis of human malignancies. In advanced melanoma, two therapeutic avenues have appeared and have immediately become the standard of care, i.e. targeted therapy with small molecule inhibitors, and immune checkpoint blockade. Sequencing has always been essential for determining which patients may benefit from targeted therapies (e.g. the presence of BRAF mutations). While sequencing does not currently help recognize which patients might benefit from immune checkpoint blockade, recent data suggest that this may change. Multiple studies have identified tumor mutation profiles associated with patients benefiting from immune checkpoint blockade therapy. These findings suggest comprehensive tumor sequencing may become a critical step for predicting therapy responses to all systemic therapies. In this review, the current and potential future impact of NGS on treatment decisions in advanced melanoma will be summarized and discussed.
Literatur
1.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409(6822):860–921.CrossRefPubMed
2.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.CrossRefPubMed
3.
Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809–19.CrossRefPubMedPubMedCentral
4.
Network Cancer Genome Atlas. Genomic classification of cutaneous melanoma. Cell. 2015;161(7):1681–96.CrossRef
5.
Stiller M, Sucker A, Griewank K, Aust D, Baretton GB, Schadendorf D, et al. Single-strand DNA library preparation improves sequencing of formalin-fixed and paraffin-embedded (FFPE) cancer DNA. Oncotarget. 2016;7(37):59115–28.PubMedPubMedCentral
6.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.CrossRefPubMedPubMedCentral
7.
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30–9.CrossRefPubMed
8.
Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. 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.CrossRefPubMed
9.
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–17.CrossRefPubMed
10.
Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.CrossRefPubMed
11.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.CrossRefPubMed
12.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.CrossRefPubMed
13.
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. doi:10.​1001/​jama.​2016.​4059.
14.
Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, 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. 2015;33(17):1889–94.CrossRefPubMedPubMedCentral
15.
Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467(7315):596–9.CrossRefPubMedPubMedCentral
16.
Kopetz S, Desai J, Chan E, Hecht JR, O’Dwyer PJ, Maru D, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol. 2015;33(34):4032–8.CrossRefPubMedPubMedCentral
17.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16.CrossRefPubMedPubMedCentral
18.
Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.CrossRefPubMed
19.
Miao D, Van Allen EM. Genomic determinants of cancer immunotherapy. Curr Opin Immunol. 2016;41:32–8.CrossRefPubMed
20.
Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.CrossRefPubMed
21.
Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33.CrossRefPubMed
22.
Kelderman S, Heemskerk B, van Tinteren H, van den Brom RR, Hospers GA, van den Eertwegh AJ, et al. Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother. 2014;63(5):449–58.PubMed
23.
Martens A, Wistuba-Hamprecht K, Foppen MG, Yuan J, Postow MA, Wong P, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res. 2016;22(12):2908–18.CrossRefPubMed
24.
Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res. 2016;22(22):5487–96.CrossRefPubMed
25.
Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116.CrossRefPubMedPubMedCentral
26.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.CrossRefPubMedPubMedCentral
27.
Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Calio A, et al. Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS One. 2015;10(6):e0130142.CrossRefPubMedPubMedCentral
28.
Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016;165(1):35–44.CrossRefPubMedPubMedCentral
29.
Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012;44(9):1006–14.CrossRefPubMedPubMedCentral
30.
Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, et al. A landscape of driver mutations in melanoma. Cell. 2012;150(2):251–63.CrossRefPubMedPubMedCentral
31.
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–99.CrossRefPubMedPubMedCentral
32.
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.CrossRefPubMedPubMedCentral
33.
McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–9.CrossRefPubMedPubMedCentral
34.
Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350(6257):207–11.CrossRefPubMedPubMedCentral
35.
Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375(9):819–29.CrossRefPubMedPubMedCentral
36.
Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science. 1995;269(5228):1281–4.CrossRefPubMed
37.
Kreiter S, Vormehr M, van de Roemer N, Diken M, Lower M, Diekmann J, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature. 2015;520(7549):692–6.CrossRefPubMedPubMedCentral
38.
Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–5.CrossRefPubMed
39.
Linnemann C, van Buuren MM, Bies L, Verdegaal EM, Schotte R, Calis JJ, et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nat Med. 2015;21(1):81–5.CrossRefPubMed
40.
41.
42.
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.CrossRefPubMedPubMedCentral
43.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8.CrossRefPubMedPubMedCentral
44.
Schumacher TN, Hacohen N. Neoantigens encoded in the cancer genome. Curr Opin Immunol. 2016;41:98–103.CrossRefPubMed
45.
Coulie PG, Lehmann F, Lethe B, Herman J, Lurquin C, Andrawiss M, et al. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic t-lymphocytes on a human-melanoma. Proc Natl Acad Sci USA. 1995;92(17):7976–80.CrossRefPubMedPubMedCentral
46.
Liepe J, Marino F, Sidney J, Jeko A, Bunting DE, Sette A, et al. A large fraction of HLA class I ligands are proteasome-generated spliced peptides. Science. 2016;354(6310):354–8.CrossRefPubMed
47.
Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515(7528):572–6.CrossRefPubMed
48.
Bassani-Sternberg M, Braunlein E, Klar R, Engleitner T, Sinitcyn P, Audehm S, et al. Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat Commun. 2016;7:13404.CrossRefPubMedPubMedCentral
49.
Tirosh I, Izar B, Prakadan SM, Wadsworth MH 2nd, Treacy D, Trombetta JJ, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016;352(6282):189–96.CrossRefPubMedPubMedCentral
50.
Gerber T, Willscher E, Loeffler-Wirth H, Hopp L, Schadendorf D, Schartl M, et al. Mapping heterogeneity in patient-derived melanoma cultures by single-cell RNA-seq. Oncotarget. 2017;8(1):846–62.PubMed
51.
Sanborn JZ, Chung J, Purdom E, Wang NJ, Kakavand H, Wilmott JS, et al. Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. Proc Natl Acad Sci USA. 2015;112(35):10995–1000.CrossRefPubMedPubMedCentral
52.
Sucker A, Zhao F, Real B, Heeke C, Bielefeld N, Mabetaen S, et al. Genetic evolution of T-cell resistance in the course of melanoma progression. Clin Cancer Res. 2014;20(24):6593–604.CrossRefPubMed
53.
Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, et al. Loss of IFN-gamma pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell. 2016;167(2):397–404.CrossRefPubMed
54.
Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6(2):202–16.CrossRefPubMed
55.
Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877–88.CrossRefPubMed
56.
Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973–7.CrossRefPubMedPubMedCentral
57.
Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, et al. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol. 2011;29(22):3085–96.CrossRefPubMedPubMedCentral
58.
Poulikakos PI, Persaud Y, Janakiraman M, Kong X, Ng C, Moriceau G, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387–90.CrossRefPubMedPubMedCentral
59.
Shi H, Moriceau G, Kong X, Lee MK, Lee H, Koya RC, et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun. 2012;3:724.CrossRefPubMedPubMedCentral
60.
Whittaker S, Kirk R, Hayward R, Zambon A, Viros A, Cantarino N, et al. Gatekeeper mutations mediate resistance to BRAF-targeted therapies. Sci Transl Med. 2010;2(35):35ra41.CrossRefPubMed
61.
Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, et al. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 2008;68(12):4853–61.CrossRefPubMedPubMedCentral
62.
Whittaker SR, Theurillat JP, Van Allen E, Wagle N, Hsiao J, Cowley GS, et al. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov. 2013;3(3):350–62.CrossRefPubMedPubMedCentral
63.
Maertens O, Johnson B, Hollstein P, Frederick DT, Cooper ZA, Messiaen L, et al. Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov. 2013;3(3):338–49.CrossRefPubMed
64.
Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature. 2010;468(7326):968–72.CrossRefPubMedPubMedCentral
65.
Paraiso KH, Xiang Y, Rebecca VW, Abel EV, Chen YA, Munko AC, et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res. 2011;71(7):2750–60.CrossRefPubMedPubMedCentral
66.
67.
Corcoran RB. New therapeutic strategies for BRAF mutant colorectal cancers. J Gastrointest Oncol. 2015;6(6):650–9.PubMedPubMedCentral
68.
Handolias D, Salemi R, Murray W, Tan A, Liu W, Viros A, et al. Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure. Pigment Cell Melanoma Res. 2010;23(2):210–5.CrossRefPubMed
69.
Kong Y, Si L, Zhu Y, Xu X, Corless CL, Flaherty KT, et al. Large-scale analysis of KIT aberrations in Chinese patients with melanoma. Clin Cancer Res. 2011;17(7):1684–91.CrossRefPubMed
70.
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.CrossRefPubMed
71.
Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu 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):2904–9.CrossRefPubMed
72.
Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez 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):3182–90.CrossRefPubMedPubMedCentral
73.
Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;305(22):2327–34.CrossRefPubMedPubMedCentral
74.
Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013;14(3):249–56.CrossRefPubMed
75.
Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, et al. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.PubMedPubMedCentral
76.
Yeh I, Botton T, Talevich E, Shain AH, Sparatta AJ, de la Fouchardiere A, et al. Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun. 2015;6:7174.CrossRefPubMedPubMedCentral
77.
Donia M, Fagone P, Nicoletti F, Andersen RS, Hogdall E, Straten PT, et al. BRAF inhibition improves tumor recognition by the immune system: potential implications for combinatorial therapies against melanoma involving adoptive T-cell transfer. Oncoimmunology. 2012;1(9):1476–83.CrossRefPubMedPubMedCentral
78.
Ilieva KM, Correa I, Josephs DH, Karagiannis P, Egbuniwe IU, Cafferkey MJ, et al. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma. Mol Cancer Ther. 2014;13(12):2769–83.CrossRefPubMedPubMedCentral
Metadaten
Titel
Next-Generation Sequencing to Guide Treatment of Advanced Melanoma
verfasst von
Klaus G. Griewank
Bastian Schilling
Publikationsdatum
01.06.2017
Verlag
Springer International Publishing
Erschienen in
American Journal of Clinical Dermatology / Ausgabe 3/2017
Print ISSN: 1175-0561
Elektronische ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-017-0260-6

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