Abstract
With increases in our understanding of the human genome and immune system, the treatment armamentarium for melanoma has benefitted from the development and approval of BRAF inhibitors, MEK inhibitors, immune checkpoint modulators via cytotoxic T-lymphocyte antigen-4 blockade, and PD-1 and PD-L1 inhibitors. These advances, however, have raised questions about combination therapy, the optimal sequential use of these agents, the limited assessment of response using traditional metrics, and the optimal selection of the population to be treated. In this review we summarize recent breakthroughs and then itemize the development of newer agents, potential prognostic and predictive biomarkers, resistance mechanisms, and strategies of combination therapy. We also emphasize the multifaceted attributes of immunotherapy in terms of durable responses and longterm survival that paradoxically necessitate further research into the underlying mechanisms and longer patient follow-up.
Keywords: Melanoma, BRAF inhibitors, MEK inhibitors, CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors, mutationdriven therapy, immunotherapy.
Graphical Abstract
[1]
Organization, W.H. Ultraviolet radiation and the INTERSUN Programme; World Health Organization: Geneva, Switzerland, 2014.
[2]
Society, A.C. Cancer Facts and Figures., 2014. [cited 2016
15.Jan]; Available from: http://www.cancer.org/acs/groups/ content/@research
[3]
Atkins, M.B.; Lotze, M.T.; Dutcher, J.P.; Fisher, R.I.; Weiss, G.; Margolin, K.; Abrams, J.; Sznol, M.; Parkinson, D.; Hawkins, M.; Paradise, C.; Kunkel, L.; Rosenberg, S.A. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J. Clin. Oncol., 1999, 17(7), 2105-2116.
[4]
Jang, S.; Atkins, M.B. Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol., 2013, 14(2), e60-e69.
[5]
Raaijmakers, M.I.; Rozati, S.; Goldinger, S.M.; Widmer, D.S.; Dummer, R.; Levesque, M.P. Melanoma immunotherapy: historical precedents, recent successes and future prospects. Immunotherapy, 2013, 5(2), 169-182.
[6]
Bittner, M.; Meltzer, P.; Chen, Y.; Jiang, Y.; Seftor, E.; Hendrix, M.; Radmacher, M.; Simon, R.; Yakhini, Z.; Ben-Dor, A.; Sampas, N.; Dougherty, E.; Wang, E.; Marincola, F.; Gooden, C.; Lueders, J.; Glatfelter, A.; Pollock, P.; Carpten, J.; Gillanders, E.; Leja, D.; Dietrich, K.; Beaudry, C.; Berens, M.; Alberts, D.; Sondak, V. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature, 2000, 406(6795), 536-540.
[7]
Cooper, Z.A.; Frederick, D.T.; Juneja, V.R.; Sullivan, R.J.; Lawrence, D.P.; Piris, A.; Sharpe, A.H.; Fisher, D.E.; Flaherty, K.T.; Wargo, J.A. BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes. OncoImmunology, 2013, 2(10), e26615.
[8]
Muñoz-Couselo, E.; García, J.S.; Pérez-García, J.M.; Cebrián, V.O.; Castán, J.C. Recent advances in the treatment of melanoma with BRAF and MEK inhibitors. Ann. Transl. Med., 2015, 3(15), 207.
[9]
Johnson, D.B.; Sosman, J.A. Update on the targeted therapy of melanoma. Curr. Treat. Options Oncol., 2013, 14(2), 280-292.
[10]
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.
[11]
Hilger, R.A.; Scheulen, M.E.; Strumberg, D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie, 2002, 25(6), 511-518.
[12]
Solit, D.B.; Garraway, L.A.; Pratilas, C.A.; Sawai, A.; Getz, G.; Basso, A.; Ye, Q.; Lobo, J.M.; She, Y.; Osman, I.; Golub, T.R.; Sebolt-Leopold, J.; Sellers, W.R.; Rosen, N. BRAF mutation predicts sensitivity to MEK inhibition. Nature, 2006, 439(7074), 358-362.
[13]
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.
[14]
Brose, M.S.; Volpe, P.; Feldman, M.; Kumar, M.; Rishi, I.; Gerrero, R.; Einhorn, E.; Herlyn, M.; Minna, J.; Nicholson, A.; Roth, J.A.; Albelda, S.M.; Davies, H.; Cox, C.; Brignell, G.; Stephens, P.; Futreal, P.A.; Wooster, R.; Stratton, M.R.; Weber, B.L. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res., 2002, 62(23), 6997-7000.
[15]
Maldonado, J.L.; Fridlyand, J.; Patel, H.; Jain, A.N.; Busam, K.; Kageshita, T.; Ono, T.; Albertson, D.G.; Pinkel, D.; Bastian, B.C. Determinants of BRAF mutations in primary melanomas. J. Natl. Cancer Inst., 2003, 95(24), 1878-1890.
[16]
Lovly, C.M.; Dahlman, K.B.; Fohn, L.E.; Su, Z.; Dias-Santagata, D.; Hicks, D.J.; Hucks, D.; Berry, E.; Terry, C.; Duke, M.; Su, Y.; Sobolik-Delmaire, T.; Richmond, A.; Kelley, M.C.; Vnencak-Jones, C.L.; Iafrate, A.J.; Sosman, J.; Pao, W. Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS One, 2012, 7(4), e35309.
[17]
Rubinstein, J.C.; Sznol, M.; Pavlick, A.C.; Ariyan, S.; Cheng, E.; Bacchiocchi, A.; Kluger, H.M.; Narayan, D.; Halaban, R. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J. Transl. Med., 2010, 8, 67.
[18]
Dahlman, K.B.; Xia, J.; Hutchinson, K.; Ng, C.; Hucks, D.; Jia, P.; Atefi, M.; Su, Z.; Branch, S.; Lyle, P.L.; Hicks, D.J.; Bozon, V.; Glaspy, J.A.; Rosen, N.; Solit, D.B.; Netterville, J.L.; Vnencak-Jones, C.L.; Sosman, J.A.; Ribas, A.; Zhao, Z.; Pao, W. BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov., 2012, 2(9), 791-797.
[19]
Tsai, J.; Lee, J.T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N.K.; Sproesser, K.; Li, L.; Smalley, K.S.; Fong, D.; Zhu, Y.L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.; Suzuki, Y.; Luu, C.; Settachatgul, C.; Shellooe, R.; Cantwell, J.; Kim, S.H.; Schlessinger, J.; Zhang, K.Y.; West, B.L.; Powell, B.; Habets, G.; Zhang, C.; Ibrahim, P.N.; Hirth, P.; Artis, D.R.; Herlyn, M.; Bollag, G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl. Acad. Sci. USA, 2008, 105(8), 3041-3046.
[20]
Curtin, J.A.; Fridlyand, J.; Kageshita, T.; Patel, H.N.; Busam, K.J.; Kutzner, H.; Cho, K.H.; Aiba, S.; Bröcker, E.B.; LeBoit, P.E.; Pinkel, D.; Bastian, B.C. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med., 2005, 353(20), 2135-2147.
[21]
Flaherty, K.T.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.A. ODwyer, 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.
[22]
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.
[23]
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. ODay, 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.
[24]
Yang, H.; Higgins, B.; Kolinsky, K.; Packman, K.; Go, Z.; Iyer, R.; Kolis, S.; Zhao, S.; Lee, R.; Grippo, J.F.; Schostack, K.; Simcox, M.E.; Heimbrook, D.; Bollag, G.; Su, F. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models. Cancer Res., 2010, 70(13), 5518-5527.
[25]
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. ODay, 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.
[26]
Su, F.; Viros, A.; Milagre, C.; Trunzer, K.; Bollag, G.; Spleiss, O.; Reis-Filho, J.S.; Kong, X.; Koya, R.C.; Flaherty, K.T.; Chapman, P.B.; Kim, M.J.; Hayward, R.; Martin, M.; Yang, H.; Wang, Q.; Hilton, H.; Hang, J.S.; Noe, J.; Lambros, M.; Geyer, F.; Dhomen, N.; Niculescu-Duvaz, I.; Zambon, A.; Niculescu-Duvaz, D.; Preece, N.; Robert, L.; Otte, N.J.; Mok, S.; Kee, D.; Ma, Y.; Zhang, C.; Habets, G.; Burton, E.A.; Wong, B.; Nguyen, H.; Kockx, M.; Andries, L.; Lestini, B.; Nolop, K.B.; Lee, R.J.; Joe, A.K.; Troy, J.L.; Gonzalez, R.; Hutson, T.E.; Puzanov, I.; Chmielowski, B.; Springer, C.J.; McArthur, G.A.; Sosman, J.A.; Lo, R.S.; Ribas, A.; Marais, R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N. Engl. J. Med., 2012, 366(3), 207-215.
[27]
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.
[28]
Zimmer, L.; Hillen, U.; Livingstone, E.; Lacouture, M.E.; Busam, K.; Carvajal, R.D.; Egberts, F.; Hauschild, A.; Kashani-Sabet, M.; Goldinger, S.M.; Dummer, R.; Long, G.V.; McArthur, G.; Scherag, A.; Sucker, A.; Schadendorf, D. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J. Clin. Oncol., 2012, 30(19), 2375-2383.
[29]
Chapman, P. Development of colonic adenomas and gastric polyps in BRAF mutant melanoma patients treated with vemurafenib. Pigment Cell Melanoma Res., 2012, 25(847), 12.
[30]
Callahan, M.K.; Rampal, R.; Harding, J.J.; Klimek, V.M.; Chung, Y.R.; Merghoub, T.; Wolchok, J.D.; Solit, D.B.; Rosen, N.; Abdel-Wahab, O.; Levine, R.L.; Chapman, P.B. Progression of RAS-mutant leukemia during RAF inhibitor treatment. N. Engl. J. Med., 2012, 367(24), 2316-2321.
[31]
Falchook, G.S.; Long, G.V.; Kurzrock, R.; Kim, K.B.; Arkenau, T.H.; Brown, M.P.; Hamid, O.; Infante, J.R.; Millward, M.; Pavlick, A.C. ODay, S.J.; Blackman, S.C.; Curtis, C.M.; Lebowitz, P.; Ma, B.; Ouellet, D.; Kefford, R.F. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet, 2012, 379(9829), 1893-1901.
[32]
Hauschild, A.; Grob, J.J.; Demidov, L.V.; Jouary, T.; Gutzmer, R.; Millward, M.; Rutkowski, P.; Blank, C.U.; Miller, W.H., Jr; Kaempgen, E.; Martín-Algarra, S.; Karaszewska, B.; Mauch, C.; Chiarion-Sileni, V.; Martin, A.M.; Swann, S.; Haney, P.; Mirakhur, B.; Guckert, M.E.; Goodman, V.; Chapman, P.B. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet, 2012, 380(9839), 358-365.
[33]
Long, G.V.; Trefzer, U.; Davies, M.A.; Kefford, R.F.; Ascierto, P.A.; Chapman, P.B.; Puzanov, I.; Hauschild, A.; Robert, C.; Algazi, A.; Mortier, L.; Tawbi, H.; Wilhelm, T.; Zimmer, L.; Switzky, J.; Swann, S.; Martin, A.M.; Guckert, M.; Goodman, V.; Streit, M.; Kirkwood, J.M.; Schadendorf, D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol., 2012, 13(11), 1087-1095.
[34]
Kudchadkar, R.; Gibney, G.; Sondak, V.K. Integrating molecular biomarkers into current clinical management in melanoma. Methods Mol. Biol., 2014, 1102, 27-42.
[35]
Conrad, W.H.; Swift, R.D.; Biechele, T.L.; Kulikauskas, R.M.; Moon, R.T.; Chien, A.J. Regulating the response to targeted MEK inhibition in melanoma: enhancing apoptosis in NRAS- and BRAF-mutant melanoma cells with Wnt/β-catenin activation. Cell Cycle, 2012, 11(20), 3724-3730.
[36]
Sullivan, R.J.; Flaherty, K. MAP kinase signaling and inhibition in melanoma. Oncogene, 2013, 32(19), 2373-2379.
[37]
Kim, K.B.; Kefford, R.; Pavlick, A.C.; Infante, J.R.; Ribas, A.; Sosman, J.A.; Fecher, L.A.; Millward, M.; McArthur, G.A.; Hwu, P.; Gonzalez, R.; Ott, P.A.; Long, G.V.; Gardner, O.S.; Ouellet, D.; Xu, Y.; DeMarini, D.J.; Le, N.T.; Patel, K.; Lewis, K.D. Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J. Clin. Oncol., 2013, 31(4), 482-489.
[38]
Infante, J.R.; Camidge, D.R.; Mileshkin, L.R.; Chen, E.X.; Hicks, R.J.; Rischin, D.; Fingert, H.; Pierce, K.J.; Xu, H.; Roberts, W.G.; Shreeve, S.M.; Burris, H.A.; Siu, L.L. Safety, pharmacokinetic, and pharmacodynamic phase I dose-escalation trial of PF-00562271, an inhibitor of focal adhesion kinase, in advanced solid tumors. J. Clin. Oncol., 2012, 30(13), 1527-1533.
[39]
Flaherty, K.T.; Robert, C.; Hersey, P.; Nathan, P.; Garbe, C.; Milhem, M.; Demidov, L.V.; Hassel, J.C.; Rutkowski, P.; Mohr, P.; Dummer, R.; Trefzer, U.; Larkin, J.M.; Utikal, J.; Dreno, B.; Nyakas, M.; Middleton, M.R.; Becker, J.C.; Casey, M.; Sherman, L.J.; Wu, F.S.; Ouellet, D.; Martin, A.M.; Patel, K.; Schadendorf, D. Improved survival with MEK inhibition in BRAF-mutated melanoma. N. Engl. J. Med., 2012, 367(2), 107-114.
[40]
Infante, J.R.; Fecher, L.A.; Falchook, G.S.; Nallapareddy, S.; Gordon, M.S.; Becerra, C.; DeMarini, D.J.; Cox, D.S.; Xu, Y.; Morris, S.R.; Peddareddigari, V.G.; Le, N.T.; Hart, L.; Bendell, J.C.; Eckhardt, G.; Kurzrock, R.; Flaherty, K.; Burris, H.A., III; Messersmith, W.A. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol., 2012, 13(8), 773-781.
[41]
Administration, U.S.F.A.D. Drug monograph: Menkinist
(trametinib), 2013. [cited 2013 May]; Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204114s000lbl.pdf n.d.
[42]
Ascierto, P.A.; Schadendorf, D.; Berking, C.; Agarwala, S.S.; van Herpen, C.M.; Queirolo, P.; Blank, C.U.; Hauschild, A.; Beck, J.T.; St-Pierre, A.; Niazi, F.; Wandel, S.; Peters, M.; Zubel, A.; Dummer, R. 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), 249-256.
[43]
Ascierto, P.A. Efficacy and safety of oral MEK162 in patients with
locally advanced and unresectable or metastatic cutaneous melanoma
harboring BRAFV600 or NRAS mutations. J. Clin. Oncol, 2012. 30. (Suppl. abstr 8511).
[44]
Kirkwood, J.M.; Bastholt, L.; Robert, C.; Sosman, J.; Larkin, J.; Hersey, P.; Middleton, M.; Cantarini, M.; Zazulina, V.; Kemsley, K.; Dummer, R. Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin. Cancer Res., 2012, 18(2), 555-567.
[45]
Robert, C.; Dummer, R.; Gutzmer, R.; Lorigan, P.; Kim, K.B.; Nyakas, M.; Arance, A.; Liszkay, G.; Schadendorf, D.; Cantarini, M.; Spencer, S.; Middleton, M.R. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study. Lancet Oncol., 2013, 14(8), 733-740.
[46]
Wagle, N.; Emery, C.; Berger, M.F.; Davis, M.J.; Sawyer, A.; Pochanard, P.; Kehoe, S.M.; Johannessen, C.M.; Macconaill, L.E.; Hahn, W.C.; Meyerson, M.; Garraway, L.A. Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J. Clin. Oncol., 2011, 29(22), 3085-3096.
[47]
Poulikakos, P.I.; Persaud, Y.; Janakiraman, M.; Kong, X.; Ng, C.; Moriceau, G.; Shi, H.; Atefi, M.; Titz, B.; Gabay, M.T.; Salton, M.; Dahlman, K.B.; Tadi, M.; Wargo, J.A.; Flaherty, K.T.; Kelley, M.C.; Misteli, T.; Chapman, P.B.; Sosman, J.A.; Graeber, T.G.; Ribas, A.; Lo, R.S.; Rosen, N.; Solit, D.B. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature, 2011, 480(7377), 387-390.
[48]
Nazarian, R.; Shi, H.; Wang, Q.; Kong, X.; Koya, R.C.; Lee, H.; Chen, Z.; Lee, M.K.; Attar, N.; Sazegar, H.; Chodon, T.; Nelson, S.F.; McArthur, G.; Sosman, J.A.; Ribas, A.; Lo, R.S. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature, 2010, 468(7326), 973-977.
[50]
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 PGC1α and MITF. Cancer Cell, 2013, 23(3), 302-315.
[51]
Pollak, M. Targeting oxidative phosphorylation: why, when, and how. Cancer Cell, 2013, 23(3), 263-264.
[52]
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. PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer Cell, 2013, 23(3), 287-301.
[53]
Yuan, P.; Ito, K.; Perez-Lorenzo, R.; Del Guzzo, C.; Lee, J.H.; Shen, C.H.; Bosenberg, M.W.; McMahon, M.; Cantley, L.C.; Zheng, B. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc. Natl. Acad. Sci. USA, 2013, 110(45), 18226-18231.
[54]
Parmenter, T.J.; Kleinschmidt, M.; Kinross, K.M.; Bond, S.T.; Li, J.; Kaadige, M.R.; Rao, A.; Sheppard, K.E.; Hugo, W.; Pupo, G.M.; Pearson, R.B.; McGee, S.L.; Long, G.V.; Scolyer, R.A.; Rizos, H.; Lo, R.S.; Cullinane, C.; Ayer, D.E.; Ribas, A.; Johnstone, R.W.; Hicks, R.J.; McArthur, G.A. Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discov., 2014, 4(4), 423-433.
[55]
Qin, J.Z.; Xin, H.; Nickoloff, B.J. Targeting glutamine metabolism sensitizes melanoma cells to TRAIL-induced death. Biochem. Biophys. Res. Commun., 2010, 398(1), 146-152.
[56]
Scott, D.A.; Richardson, A.D.; Filipp, F.V.; Knutzen, C.A.; Chiang, G.G.; Ronai, Z.A.; Osterman, A.L.; Smith, J.W. Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. J. Biol. Chem., 2011, 286(49), 42626-42634.
[58]
Hoeflich, K.P.; Merchant, M.; Orr, C.; Chan, J.; Den Otter, D.; Berry, L.; Kasman, I.; Koeppen, H.; Rice, K.; Yang, N.Y.; Engst, S.; Johnston, S.; Friedman, L.S.; Belvin, M. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res., 2012, 72(1), 210-219.
[59]
Flaherty, K.T.; Infante, J.R.; Daud, A.; Gonzalez, R.; Kefford, R.F.; Sosman, J.; Hamid, O.; Schuchter, L.; Cebon, J.; Ibrahim, N.; Kudchadkar, R.; Burris, H.A., III; Falchook, G.; Algazi, A.; Lewis, K.; Long, G.V.; Puzanov, I.; Lebowitz, P.; Singh, A.; Little, S.; Sun, P.; Allred, A.; Ouellet, D.; Kim, K.B.; Patel, K.; Weber, J. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med., 2012, 367(18), 1694-1703.
[60]
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.
[61]
Paraiso, K.H.; Fedorenko, I.V.; Cantini, L.P.; Munko, A.C.; Hall, M.; Sondak, V.K.; Messina, J.L.; Flaherty, K.T.; Smalley, K.S. Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy. Br. J. Cancer, 2010, 102(12), 1724-1730.
[62]
Robert, C.; Karaszewska, B.; Schachter, J.; Rutkowski, P.; Mackiewicz, A.; Stroiakovski, D.; Lichinitser, M.; Dummer, R.; Grange, F.; Mortier, L.; Chiarion-Sileni, V.; Drucis, K.; Krajsova, I.; Hauschild, A.; Lorigan, P.; Wolter, P.; Long, G.V.; Flaherty, K.; Nathan, P.; Ribas, A.; Martin, A.M.; Sun, P.; Crist, W.; Legos, J.; Rubin, S.D.; Little, S.M.; Schadendorf, D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med., 2015, 372(1), 30-39.
[63]
Long, G.V.; Stroyakovskiy, D.; Gogas, H.; Levchenko, E.; de Braud, F.; Larkin, J.; Garbe, C.; Jouary, T.; Hauschild, A.; Grob, J.J.; Chiarion-Sileni, V.; Lebbe, C.; Mandalà, M.; Millward, M.; Arance, A.; Bondarenko, I.; Haanen, J.B.; Hansson, J.; Utikal, J.; Ferraresi, V.; Kovalenko, N.; Mohr, P.; Probachai, V.; Schadendorf, D.; Nathan, P.; Robert, C.; Ribas, A.; DeMarini, D.J.; Irani, J.G.; Swann, S.; Legos, J.J.; 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), 444-451.
[64]
Ascierto, P.A. coBRIM: a phase 3, double-blind, placebo-controlled study of vemurafenib versus vemurafenib+ cobimetinib in previously untreated BRAFV600 mutation–positive patients with unresectable locally advanced or metastatic melanoma (NCT01689519). J. Transl. Med., 2015, 13(Suppl. 1), O4.
[65]
Wagle, N.; Van Allen, E.M.; Treacy, D.J.; Frederick, D.T.; Cooper, Z.A.; Taylor-Weiner, A.; Rosenberg, M.; Goetz, E.M.; Sullivan, R.J.; Farlow, D.N.; Friedrich, D.C.; Anderka, K.; Perrin, D.; Johannessen, C.M.; McKenna, A.; Cibulskis, K.; Kryukov, G.; Hodis, E.; Lawrence, D.P.; Fisher, S.; Getz, G.; Gabriel, S.B.; Carter, S.L.; Flaherty, K.T.; Wargo, J.A.; Garraway, L.A. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov., 2014, 4(1), 61-68.
[66]
Long, G.V.; Fung, C.; Menzies, A.M.; Pupo, G.M.; Carlino, M.S.; Hyman, J.; Shahheydari, H.; Tembe, V.; Thompson, J.F.; Saw, R.P.; Howle, J.; Hayward, N.K.; Johansson, P.; Scolyer, R.A.; Kefford, R.F.; Rizos, H. Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat. Commun., 2014, 5, 5694.
[67]
Carlino, M.S.; Todd, J.R.; Gowrishankar, K.; Mijatov, B.; Pupo, G.M.; Fung, C.; Snoyman, S.; Hersey, P.; Long, G.V.; Kefford, R.F.; Rizos, H. Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma. Mol. Oncol., 2014, 8(3), 544-554.
[68]
Moriceau, G.; Hugo, W.; Hong, A.; Shi, H.; Kong, X.; Yu, C.C.; Koya, R.C.; Samatar, A.A.; Khanlou, N.; Braun, J.; Ruchalski, K.; Seifert, H.; Larkin, J.; Dahlman, K.B.; Johnson, D.B.; Algazi, A.; Sosman, J.A.; Ribas, A.; Lo, R.S. Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction. Cancer Cell, 2015, 27(2), 240-256.
[69]
Goldinger, S.M.; Zimmer, L.; Schulz, C.; Ugurel, S.; Hoeller, C.; Kaehler, K.C.; Schadendorf, D.; Hassel, J.C.; Becker, J.; Hauschild, A.; Dummer, R. Upstream mitogen-activated protein kinase (MAPK) pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients. Eur. J. Cancer, 2014, 50(2), 406-410.
[70]
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.
[71]
Rosenberg, S.A.; Mulé, J.J.; Spiess, P.J.; Reichert, C.M.; Schwarz, S.L. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J. Exp. Med., 1985, 161(5), 1169-1188.
[72]
Eklund, J.W.; Kuzel, T.M. A review of recent findings involving interleukin-2-based cancer therapy. Curr. Opin. Oncol., 2004, 16(6), 542-546.
[73]
Printz, C. Spontaneous regression of melanoma may offer insight into cancer immunology. J. Natl. Cancer Inst., 2001, 93(14), 1047-1048.
[74]
McDermott, D.; Lebbé, C.; Hodi, F.S.; Maio, M.; Weber, J.S.; Wolchok, J.D.; Thompson, J.A.; Balch, C.M. Durable benefit and the potential for long-term survival with immunotherapy in advanced melanoma. Cancer Treat. Rev., 2014, 40(9), 1056-1064.
[75]
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.
[76]
Schwartzentruber, D.J.; Lawson, D.H.; Richards, J.M.; Conry, R.M.; Miller, D.M.; Treisman, J.; Gailani, F.; Riley, L.; Conlon, K.; Pockaj, B.; Kendra, K.L.; White, R.L.; Gonzalez, R.; Kuzel, T.M.; Curti, B.; Leming, P.D.; Whitman, E.D.; Balkissoon, J.; Reintgen, D.S.; Kaufman, H.; Marincola, F.M.; Merino, M.J.; Rosenberg, S.A.; Choyke, P.; Vena, D.; Hwu, P. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N. Engl. J. Med., 2011, 364(22), 2119-2127.
[77]
Schwartz, R.N.; Stover, L.; Dutcher, J. Managing toxicities of high-dose interleukin-2. Oncology (Williston Park), 2002, 16(11)(Suppl. 13), 11-20.
[78]
Waterhouse, P.; Penninger, J.M.; Timms, E.; Wakeham, A.; Shahinian, A.; Lee, K.P.; Thompson, C.B.; Griesser, H.; Mak, T.W. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 1995, 270(5238), 985-988.
[79]
Harding, F.A.; McArthur, J.G.; Gross, J.A.; Raulet, D.H.; Allison, J.P. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature, 1992, 356(6370), 607-609.
[80]
Linsley, P.S.; Bradshaw, J.; Greene, J.; Peach, R.; Bennett, K.L.; Mittler, R.S. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity, 1996, 4(6), 535-543.
[81]
Salama, A.K.; Hodi, F.S. Cytotoxic T-lymphocyte-associated antigen-4. Clin. Cancer Res., 2011, 17(14), 4622-4628.
[82]
Peggs, K.S.; Quezada, S.A.; Korman, A.J.; Allison, J.P. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr. Opin. Immunol., 2006, 18(2), 206-213.
[83]
Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science, 1996, 271(5256), 1734-1736.
[84]
Phan, G.Q.; Yang, J.C.; Sherry, R.M.; Hwu, P.; Topalian, S.L.; Schwartzentruber, D.J.; Restifo, N.P.; Haworth, L.R.; Seipp, C.A.; Freezer, L.J.; Morton, K.E.; Mavroukakis, S.A.; Duray, P.H.; Steinberg, S.M.; Allison, J.P.; Davis, T.A.; Rosenberg, S.A. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8372-8377.
[85]
Administration, U.S.F.A.D. FDA labeling information, 2011. [cited
2016 mars]; Available from: http://www.accessdata.fda.gov/ drugsatfdadocs/ label/2011/125377s0000lbl.pdf
[86]
Hodi, F.S. ODay, 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.; Lebbé, 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.
[87]
Robert, C.; Thomas, L.; Bondarenko, I. ODay, S.; Weber, 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.
[88]
Maio, M.; Grob, J.J.; Aamdal, S.; Bondarenko, I.; Robert, C.; Thomas, L.; Garbe, C.; Chiarion-Sileni, V.; Testori, A.; Chen, T.T.; Tschaika, M.; Wolchok, J.D. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J. Clin. Oncol., 2015, 33(10), 1191-1196.
[89]
Wolchok, J.D.; Weber, J.S.; Maio, M.; Neyns, B.; Harmankaya, K.; Chin, K.; Cykowski, L.; de Pril, V.; Humphrey, R.; Lebbé, C. Long-term survival in patients with metastatic melanoma who received
ipilimumab in four phase II trials. in ASCO Annual Meeting
Proceedings. 2013.
[90]
Schadendorf, D.; Hodi, F.S.; Robert, C.; Weber, J.S.; Margolin, K.; Hamid, O.; Patt, D.; Chen, T.T.; Berman, D.M.; Wolchok, J.D. 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), 1889-1894.
[91]
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), 166-172.
[92]
Ribas, A.; Chmielowski, B.; Glaspy, J.A. Do we need a different set of response assessment criteria for tumor immunotherapy? Clin. Cancer Res., 2009, 15(23), 7116-7118.
[93]
Wolchok, J.D.; Hoos, A. ODay, S.; Weber, J.S.; Hamid, O.; Lebbé, C.; Maio, M.; Binder, M.; Bohnsack, O.; Nichol, G.; Humphrey, R.; Hodi, F.S. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res., 2009, 15(23), 7412-7420.
[94]
Weber, J.; Thompson, J.A.; Hamid, O.; Minor, D.; Amin, A.; Ron, I.; Ridolfi, R.; Assi, H.; Maraveyas, A.; Berman, D.; Siegel, J. ODay, S.J. A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin. Cancer Res., 2009, 15(17), 5591-5598.
[95]
ODay 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.
[96]
Camacho, L.H.; Antonia, S.; Sosman, J.; Kirkwood, J.M.; Gajewski, T.F.; Redman, B.; Pavlov, D.; Bulanhagui, C.; Bozon, V.A.; Gomez-Navarro, J.; Ribas, A. Phase I/II trial of tremelimumab in patients with metastatic melanoma. J. Clin. Oncol., 2009, 27(7), 1075-1081.
[97]
Kirkwood, J.M.; Lorigan, P.; Hersey, P.; Hauschild, A.; Robert, C.; McDermott, D.; Marshall, M.A.; Gomez-Navarro, J.; Liang, J.Q.; Bulanhagui, C.A. Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. Clin. Cancer Res., 2010, 16(3), 1042-1048.
[98]
Ribas, A. Phase III, open-label, randomized, comparative study of
tremelimumab (CP-675,206) and chemotherapy (te-mozolomide
[TMZ] or dacarbazine [DTIC]) in patients with advanced
melanoma. ASCO Annual Meeting Proceedings, 2008.
[99]
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.
[100]
Tarhini, A.A.; Cherian, J.; Moschos, S.J.; Tawbi, H.A.; Shuai, Y.; Gooding, W.E.; Sander, C.; Kirkwood, J.M. Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J. Clin. Oncol., 2012, 30(3), 322-328.
[101]
Chen, L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol., 2004, 4(5), 336-347.
[102]
Freeman, G.J.; Long, A.J.; Iwai, Y.; Bourque, K.; Chernova, T.; Nishimura, H.; Fitz, L.J.; Malenkovich, N.; Okazaki, T.; Byrne, M.C.; Horton, H.F.; Fouser, L.; Carter, L.; Ling, V.; Bowman, M.R.; Carreno, B.M.; Collins, M.; Wood, C.R.; Honjo, T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med., 2000, 192(7), 1027-1034.
[103]
Okazaki, T.; Iwai, Y.; Honjo, T. New regulatory co-receptors: inducible co-stimulator and PD-1. Curr. Opin. Immunol., 2002, 14(6), 779-782.
[104]
Sharpe, A.H.; Wherry, E.J.; Ahmed, R.; Freeman, G.J. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat. Immunol., 2007, 8(3), 239-245.
[105]
Dong, H.; Zhu, G.; Tamada, K.; Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med., 1999, 5(12), 1365-1369.
[106]
Tseng, S.Y.; Otsuji, M.; Gorski, K.; Huang, X.; Slansky, J.E.; Pai, S.I.; Shalabi, A.; Shin, T.; Pardoll, D.M.; Tsuchiya, H. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J. Exp. Med., 2001, 193(7), 839-846.
[107]
Latchman, Y.; Wood, C.R.; Chernova, T.; Chaudhary, D.; Borde, M.; Chernova, I.; Iwai, Y.; Long, A.J.; Brown, J.A.; Nunes, R.; Greenfield, E.A.; Bourque, K.; Boussiotis, V.A.; Carter, L.L.; Carreno, B.M.; Malenkovich, N.; Nishimura, H.; Okazaki, T.; Honjo, T.; Sharpe, A.H.; Freeman, G.J. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol., 2001, 2(3), 261-268.
[108]
Topalian, S.L.; Hodi, F.S.; Brahmer, J.R.; Gettinger, S.N.; Smith, D.C.; McDermott, D.F.; Powderly, J.D.; Carvajal, R.D.; Sosman, J.A.; Atkins, M.B.; Leming, P.D.; Spigel, D.R.; Antonia, S.J.; Horn, L.; Drake, C.G.; Pardoll, D.M.; Chen, L.; Sharfman, W.H.; Anders, R.A.; Taube, J.M.; McMiller, T.L.; Xu, H.; Korman, A.J.; Jure-Kunkel, M.; Agrawal, S.; McDonald, D.; Kollia, G.D.; Gupta, A.; Wigginton, J.M.; Sznol, M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med., 2012, 366(26), 2443-2454.
[109]
Kim, J.; Myers, A.C.; Chen, L.; Pardoll, D.M.; Truong-Tran, Q.A.; Lane, A.P.; McDyer, J.F.; Fortuno, L.; Schleimer, R.P. Constitutive and inducible expression of b7 family of ligands by human airway epithelial cells. Am. J. Respir. Cell Mol. Biol., 2005, 33(3), 280-289.
[110]
Petroff, M.G.; Chen, L.; Phillips, T.A.; Azzola, D.; Sedlmayr, P.; Hunt, J.S. B7 family molecules are favorably positioned at the human maternal-fetal interface. Biol. Reprod., 2003, 68(5), 1496-1504.
[111]
Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; Lennon, V.A.; Celis, E.; Chen, L. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med., 2002, 8(8), 793-800.
[112]
Pedoeem, A.; Azoulay-Alfaguter, I.; Strazza, M.; Silverman, G.J.; Mor, A. Programmed death-1 pathway in cancer and autoimmunity. Clin. Immunol., 2014, 153(1), 145-152.
[113]
Hamanishi, J.; Mandai, M.; Iwasaki, M.; Okazaki, T.; Tanaka, Y.; Yamaguchi, K.; Higuchi, T.; Yagi, H.; Takakura, K.; Minato, N.; Honjo, T.; Fujii, S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl. Acad. Sci. USA, 2007, 104(9), 3360-3365.
[114]
Thompson, R.H.; Kuntz, S.M.; Leibovich, B.C.; Dong, H.; Lohse, C.M.; Webster, W.S.; Sengupta, S.; Frank, I.; Parker, A.S.; Zincke, H.; Blute, M.L.; Sebo, T.J.; Cheville, J.C.; Kwon, E.D. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res., 2006, 66(7), 3381-3385.
[115]
Hino, R.; Kabashima, K.; Kato, Y.; Yagi, H.; Nakamura, M.; Honjo, T.; Okazaki, T.; Tokura, Y. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer, 2010, 116(7), 1757-1766.
[116]
Taube, J.M. Colocalization of inflammatory response with B7-h1 expres-sion in human melanocytic lesions supports an adaptive re-sistance mechanism of immune escape. Sci. Transl. Med, 2012. 4(127), 127ra37-127ra37.
[117]
Brahmer, J.R.; Drake, C.G.; Wollner, I.; Powderly, J.D.; Picus, J.; Sharfman, W.H.; Stankevich, E.; Pons, A.; Salay, T.M.; McMiller, T.L.; Gilson, M.M.; Wang, C.; Selby, M.; Taube, J.M.; Anders, R.; Chen, L.; Korman, A.J.; Pardoll, D.M.; Lowy, I.; Topalian, S.L. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol., 2010, 28(19), 3167-3175.
[118]
Weber, J.S.; Kudchadkar, R.R.; Yu, B.; Gallenstein, D.; Horak, C.E.; Inzunza, H.D.; Zhao, X.; Martinez, A.J.; Wang, W.; Gibney, G.; Kroeger, J.; Eysmans, C.; Sarnaik, A.A.; Chen, Y.A. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J. Clin. Oncol., 2013, 31(34), 4311-4318.
[119]
Weber, J.; D’Angelo, S.; Gutzmer, R. A phase 3 randomized, open-label study of nivolumab versus investigator’s choice of chemotherapy in patients with advanced melanoma after prior anti-CTLA4 therapy. Ann. Oncol., 2014.
[120]
Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; Savage, K.J.; Hernberg, M.M.; Lebbé, C.; Charles, J.; Mihalcioiu, C.; Chiarion-Sileni, V.; Mauch, C.; Cognetti, F.; Arance, A.; Schmidt, H.; Schadendorf, D.; Gogas, H.; Lundgren-Eriksson, L.; Horak, C.; Sharkey, B.; Waxman, I.M.; Atkinson, V.; Ascierto, P.A. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med., 2015, 372(4), 320-330.
[121]
Brahmer, J.R.; Tykodi, S.S.; Chow, L.Q.; Hwu, W.J.; Topalian, S.L.; Hwu, P.; Drake, C.G.; Camacho, L.H.; Kauh, J.; Odunsi, K.; Pitot, H.C.; Hamid, O.; Bhatia, S.; Martins, R.; Eaton, K.; Chen, S.; Salay, T.M.; Alaparthy, S.; Grosso, J.F.; Korman, A.J.; Parker, S.M.; Agrawal, S.; Goldberg, S.M.; Pardoll, D.M.; Gupta, A.; Wigginton, J.M. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med., 2012, 366(26), 2455-2465.
[122]
Hamid, O.; Robert, C.; Daud, A.; Hodi, F.S.; Hwu, W.J.; Kefford, R.; Wolchok, J.D.; Hersey, P.; Joseph, R.W.; Weber, J.S.; Dronca, R.; Gangadhar, T.C.; Patnaik, A.; Zarour, H.; Joshua, A.M.; Gergich, K.; Elassaiss-Schaap, J.; Algazi, A.; Mateus, C.; Boasberg, P.; Tumeh, P.C.; Chmielowski, B.; Ebbinghaus, S.W.; Li, X.N.; Kang, S.P.; Ribas, A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med., 2013, 369(2), 134-144.
[123]
Masters, G.A. Clinical cancer advances 2015: Annual report on progress against cancer from the American Society of Clinical Oncology. J. Clin. Oncol., 2015, 33(7), 786-809.
[124]
Ribas, A.; Puzanov, I.; Dummer, R.; Schadendorf, D.; Hamid, O.; Robert, C.; Hodi, F.S.; Schachter, J.; Pavlick, A.C.; Lewis, K.D.; Cranmer, L.D.; Blank, C.U. ODay, S.J.; Ascierto, P.A.; Salama, A.K.; Margolin, K.A.; Loquai, C.; Eigentler, T.K.; Gangadhar, T.C.; Carlino, M.S.; Agarwala, S.S.; Moschos, S.J.; Sosman, J.A.; Goldinger, S.M.; Shapira-Frommer, R.; Gonzalez, R.; Kirkwood, J.M.; Wolchok, J.D.; Eggermont, A.; Li, X.N.; Zhou, W.; Zernhelt, A.M.; Lis, J.; Ebbinghaus, S.; Kang, S.P.; Daud, A. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol., 2015, 16(8), 908-918.
[125]
Robert, C.; Ribas, A.; Wolchok, J.D.; Hodi, F.S.; Hamid, O.; Kefford, R.; Weber, J.S.; Joshua, A.M.; Hwu, W.J.; Gangadhar, T.C.; Patnaik, A.; Dronca, R.; Zarour, H.; Joseph, R.W.; Boasberg, P.; Chmielowski, B.; Mateus, C.; Postow, M.A.; Gergich, K.; Elassaiss-Schaap, J.; Li, X.N.; Iannone, R.; Ebbinghaus, S.W.; Kang, S.P.; Daud, A. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet, 2014, 384(9948), 1109-1117.
[126]
Robert, L.; Tsoi, J.; Wang, X.; Emerson, R.; Homet, B.; Chodon, T.; Mok, S.; Huang, R.R.; Cochran, A.J.; Comin-Anduix, B.; Koya, R.C.; Graeber, T.G.; Robins, H.; Ribas, A. CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin. Cancer Res., 2014, 20(9), 2424-2432.
[127]
Cha, E. Improved survival with T cell clonotype stability after anti–
CTLA-4 treatment in cancer patients. Sci. Transla. Med, 2014. 6(238), 238ra70.
[128]
Kvistborg, P. Anti–CTLA-4 therapy broadens the melanomareactive
CD8+ T cell response. Sci. Transla. Med, 2014. 6(254),
254ra128.
[129]
Huang, R.R.; Jalil, J.; Economou, J.S.; Chmielowski, B.; Koya, R.C.; Mok, S.; Sazegar, H.; Seja, E.; Villanueva, A.; Gomez-Navarro, J.; Glaspy, J.A.; Cochran, A.J.; Ribas, A. CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans. Clin. Cancer Res., 2011, 17(12), 4101-4109.
[130]
Herbst, R.S.; Soria, J.C.; Kowanetz, M.; Fine, G.D.; Hamid, O.; Gordon, M.S.; Sosman, J.A.; McDermott, D.F.; Powderly, J.D.; Gettinger, S.N.; Kohrt, H.E.; Horn, L.; Lawrence, D.P.; Rost, S.; Leabman, M.; Xiao, Y.; Mokatrin, A.; Koeppen, H.; Hegde, P.S.; Mellman, I.; Chen, D.S.; Hodi, F.S. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528), 563-567.
[131]
Robert, L.; Harview, C.; Emerson, R.; Wang, X.; Mok, S.; Homet, B.; Comin-Anduix, B.; Koya, R.C.; Robins, H.; Tumeh, P.C.; Ribas, A. Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes. OncoImmunology, 2014, 3(6), e29244.
[132]
Tumeh, P.C.; Harview, C.L.; Yearley, J.H.; Shintaku, I.P.; Taylor, E.J.; Robert, L.; Chmielowski, B.; Spasic, M.; Henry, G.; Ciobanu, V.; West, A.N.; Carmona, M.; Kivork, C.; Seja, E.; Cherry, G.; Gutierrez, A.J.; Grogan, T.R.; Mateus, C.; Tomasic, G.; Glaspy, J.A.; Emerson, R.O.; Robins, H.; Pierce, R.H.; Elashoff, D.A.; Robert, C.; Ribas, A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 2014, 515(7528), 568-571.
[133]
Spranger, S. Up-regulation of PD-L1, IDO, and Tregs in the melanoma
tu-mor microenvironment is driven by CD8+ T cells. Sci.
Transla. Med, 2013. 5(200), 200ra116.
[134]
Bald, T.; Landsberg, J.; Lopez-Ramos, D.; Renn, M.; Glodde, N.; Jansen, P.; Gaffal, E.; Steitz, J.; Tolba, R.; Kalinke, U.; Limmer, A.; Jönsson, G.; Hölzel, M.; Tüting, T. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov., 2014, 4(6), 674-687.
[135]
Weber, J.S.; Kähler, K.C.; Hauschild, A. Management of immune-related adverse events and kinetics of response with ipilimumab. J. Clin. Oncol., 2012, 30(21), 2691-2697.
[136]
Robert, C.; Schachter, J.; Long, G.V.; Arance, A.; Grob, J.J.; Mortier, L.; Daud, A.; Carlino, M.S.; McNeil, C.; Lotem, M.; Larkin, J.; Lorigan, P.; Neyns, B.; Blank, C.U.; Hamid, O.; Mateus, C.; Shapira-Frommer, R.; Kosh, M.; Zhou, H.; Ibrahim, N.; Ebbinghaus, S.; Ribas, A. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med., 2015, 372(26), 2521-2532.
[137]
Ribas, A. P0116 Updated clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in 411 patients with melanoma. Eur. J. Cancer, 2015, 51, e24.
[138]
Dummer, R. A randomized controlled comparison of pembrolizumab and chemotherapy in patients with ipilimumab-refractory melanoma. J. Transl. Med., 2015, 13(Suppl. 1), O5.
[139]
Robert, C. Lba34pembrolizumab (pembro; mk-3475) for advanced mela-noma (mel): randomized comparison of two dosing schedules. Ann. Oncol., 2014, 25(Suppl. 4), 438-442.
[140]
Ascierto, P.A.; Simeone, E.; Giannarelli, D.; Grimaldi, A.M.; Romano, A.; Mozzillo, N. Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J. Transl. Med., 2012, 10(1), 107.
[141]
Ackerman, A.; Klein, O.; McDermott, D.F.; Wang, W.; Ibrahim, N.; Lawrence, D.P.; Gunturi, A.; Flaherty, K.T.; Hodi, F.S.; Kefford, R.; Menzies, A.M.; Atkins, M.B.; Long, G.V.; Sullivan, R.J. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer, 2014, 120(11), 1695-1701.
[142]
Farolfi, A.; Ridolfi, L.; Guidoboni, M.; Nicoletti, S.V.; Piciucchi, S.; Valmorri, L.; Costantini, M.; Scarpi, E.; Amadori, D.; Ridolfi, R. Ipilimumab in advanced melanoma: reports of long-lasting responses. Melanoma Res., 2012, 22(3), 263-270.
[143]
Kaufman, H.L.; Kirkwood, J.M.; Hodi, F.S.; Agarwala, S.; Amatruda, T.; Bines, S.D.; Clark, J.I.; Curti, B.; Ernstoff, M.S.; Gajewski, T.; Gonzalez, R.; Hyde, L.J.; Lawson, D.; Lotze, M.; Lutzky, J.; Margolin, K.; McDermott, D.F.; Morton, D.; Pavlick, A.; Richards, J.M.; Sharfman, W.; Sondak, V.K.; Sosman, J.; Steel, S.; Tarhini, A.; Thompson, J.A.; Titze, J.; Urba, W.; White, R.; Atkins, M.B. The Society for Immunotherapy of Cancer consensus statement on tumour immunotherapy for the treatment of cutaneous melanoma. Nat. Rev. Clin. Oncol., 2013, 10(10), 588-598.
[144]
Callahan, M.K.; Masters, G.; Pratilas, C.A.; Ariyan, C.; Katz, J.; Kitano, S.; Russell, V.; Gordon, R.A.; Vyas, S.; Yuan, J.; Gupta, A.; Wigginton, J.M.; Rosen, N.; Merghoub, T.; Jure-Kunkel, M.; Wolchok, J.D. Paradoxical activation of T cells via augmented ERK signaling mediated by a RAF inhibitor. Cancer Immunol. Res., 2014, 2(1), 70-79.
[145]
Frederick, D.T.; Piris, A.; Cogdill, A.P.; Cooper, Z.A.; Lezcano, C.; Ferrone, C.R.; Mitra, D.; Boni, A.; Newton, L.P.; Liu, C.; Peng, W.; Sullivan, R.J.; Lawrence, D.P.; Hodi, F.S.; Overwijk, W.W.; Lizée, G.; Murphy, G.F.; Hwu, P.; Flaherty, K.T.; Fisher, D.E.; Wargo, J.A. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin. Cancer Res., 2013, 19(5), 1225-1231.
[146]
Boni, A.; Cogdill, A.P.; Dang, P.; Udayakumar, D.; Njauw, C.N.; Sloss, C.M.; Ferrone, C.R.; Flaherty, K.T.; Lawrence, D.P.; Fisher, D.E.; Tsao, H.; Wargo, J.A. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res., 2010, 70(13), 5213-5219.
[147]
Comin-Anduix, B.; Chodon, T.; Sazegar, H.; Matsunaga, D.; Mock, S.; Jalil, J.; Escuin-Ordinas, H.; Chmielowski, B.; Koya, R.C.; Ribas, A. The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations. Clin. Cancer Res., 2010, 16(24), 6040-6048.
[148]
Ott, P.A.; Bhardwaj, N. Impact of MAPK pathway activation in BRAFV600 melanoma on T cell and dendritic cell function. Front. Immunol., 2013, 4, 346.
[149]
Koya, R.C.; Mok, S.; Otte, N.; Blacketor, K.J.; Comin-Anduix, B.; Tumeh, P.C.; Minasyan, A.; Graham, N.A.; Graeber, T.G.; Chodon, T.; Ribas, A. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res., 2012, 72(16), 3928-3937.
[150]
Sumimoto, H.; Imabayashi, F.; Iwata, T.; Kawakami, Y. The BRAF-MAPK signaling pathway is essential for cancer-immune evasion in human melanoma cells. J. Exp. Med., 2006, 203(7), 1651-1656.
[151]
Wilmott, J.S.; Long, G.V.; Howle, J.R.; Haydu, L.E.; Sharma, R.N.; Thompson, J.F.; Kefford, R.F.; Hersey, P.; Scolyer, R.A. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin. Cancer Res., 2012, 18(5), 1386-1394.
[152]
Atefi, M.; Avramis, E.; Lassen, A.; Wong, D.J.; Robert, L.; Foulad, D.; Cerniglia, M.; Titz, B.; Chodon, T.; Graeber, T.G.; Comin-Anduix, B.; Ribas, A. Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin. Cancer Res., 2014, 20(13), 3446-3457.
[153]
Powderly, J.; Koeppen, H.; Hodi, F.S.; Sosman, J.; Gettinger, S.; Desai, R.; Tabernero, J.; Soria, J.C.; Hamid, O.; Fine, G.; Xiao, Y.; Mokatrin, A.; Wu, J.; Anderson, M.; Irving, B.; Chen, D.S.; Kowanetz, M. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. ASCO Annual Meeting Proceedings 2013.
[154]
Cooper, Z.A.; Juneja, V.R.; Sage, P.T.; Frederick, D.T.; Piris, A.; Mitra, D.; Lo, J.A.; Hodi, F.S.; Freeman, G.J.; Bosenberg, M.W.; McMahon, M.; Flaherty, K.T.; Fisher, D.E.; Sharpe, A.H.; Wargo, J.A. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol. Res., 2014, 2(7), 643-654.
[155]
Ribas, A.; Hodi, F.S.; Callahan, M.; Konto, C.; Wolchok, J. Hepatotoxicity with combination of vemurafenib and ipilimumab. N. Engl. J. Med., 2013, 368(14), 1365-1366.
[156]
Puzanov, I. Phase 1 study of the BRAF inhibitor dabrafenib (D)
with or without the MEK inhibitor trametinib (T) in combination
with ipilimumab (Ipi) for V600E/K mutation-positive unresectable
or metastatic melanoma (MM). ASCO Annual Meeting Proceedings, 2014.
[157]
Luke, J.J.; Hodi, F.S. Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Oncologist, 2013, 18(6), 717-725.
[158]
Zitvogel, L.; Apetoh, L.; Ghiringhelli, F.; Kroemer, G. Immunological aspects of cancer chemotherapy. Nat. Rev. Immunol., 2008, 8(1), 59-73.
[159]
Ascierto, P.A.; Minor, D.; Ribas, A.; Lebbe, C. OHagan, A.; Arya, N.; Guckert, M.; Schadendorf, D.; Kefford, R.F.; Grob, J.J.; Hamid, O.; Amaravadi, R.; Simeone, E.; Wilhelm, T.; Kim, K.B.; Long, G.V.; Martin, A.M.; Mazumdar, J.; Goodman, V.L.; Trefzer, U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J. Clin. Oncol., 2013, 31(26), 3205-3211.
[160]
Tuma, R.S. Melanoma: Two Experts on Their First-Line Treatment Choices for Patients with Advanced Disease: Start with the Tortoise or the Hare? Oncol. Times, 2012, 34(1), 7-8.
[161]
Bhatia, S.; Tykodi, S.S.; Thompson, J.A. Treatment of metastatic melanoma: an overview. Oncology (Huntingt.), 2009, 23(6), 488-496.
[162]
Minor, D.R.; Moore, D.; Kim, C.; Kashani-Sabet, M.; Venna, S.S.; Wang, W.; Boasberg, P. ODay, S. Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy. Oncologist, 2009, 14(10), 995-1002.
[163]
Patel, J.D.; Krilov, L.; Adams, S.; Aghajanian, C.; Basch, E.; Brose, M.S.; Carroll, W.L.; de Lima, M.; Gilbert, M.R.; Kris, M.G.; Marshall, J.L.; Masters, G.A. ODay, S.J.; Polite, B.; Schwartz, G.K.; Sharma, S.; Thompson, I.; Vogelzang, N.J.; Roth, B.J. Clinical cancer advances 2013: annual report on progress against cancer from the American Society of Clinical Oncology. J. Clin. Oncol., 2014, 32(2), 129-160.
[164]
Khalili, J.S.; Liu, S.; Rodríguez-Cruz, T.G.; Whittington, M.; Wardell, S.; Liu, C.; Zhang, M.; Cooper, Z.A.; Frederick, D.T.; Li, Y.; Zhang, M.; Joseph, R.W.; Bernatchez, C.; Ekmekcioglu, S.; Grimm, E.; Radvanyi, L.G.; Davis, R.E.; Davies, M.A.; Wargo, J.A.; Hwu, P.; Lizée, G. Oncogenic BRAF(V600E) promotes stromal cell-mediated immunosuppression via induction of interleukin-1 in melanoma. Clin. Cancer Res., 2012, 18(19), 5329-5340.
[165]
Liu, C.; Peng, W.; Xu, C.; Lou, Y.; Zhang, M.; Wargo, J.A.; Chen, J.Q.; Li, H.S.; Watowich, S.S.; Yang, Y.; Tompers Frederick, D.; Cooper, Z.A.; Mbofung, R.M.; Whittington, M.; Flaherty, K.T.; Woodman, S.E.; Davies, M.A.; Radvanyi, L.G.; Overwijk, W.W.; Lizée, G.; Hwu, P. BRAF inhibition increases tumor infiltration by T cells and enhances the antitumor activity of adoptive immunotherapy in mice. Clin. Cancer Res., 2013, 19(2), 393-403.
[166]
Jiang, X.; Zhou, J.; Giobbie-Hurder, A.; Wargo, J.; Hodi, F.S. The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin. Cancer Res., 2013, 19(3), 598-609.
[167]
Curran, M.A.; Montalvo, W.; Yagita, H.; Allison, J.P. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc. Natl. Acad. Sci. USA, 2010, 107(9), 4275-4280.
[168]
Selby, M.; Engelhardt, J.; Lu, L-S.; Quigley, M.; Wang, C.; Chen, B.; Korman, A.J.; Squibb, B-M. Antitumor activity of concurrent
blockade of immune checkpoint molecules CTLA-4 and PD-1 in
preclinical models. J. Clin. Oncol, 2013. (supple. abstr 3061).
[169]
Nirschl, C.J.; Drake, C.G. Molecular pathways: coexpression of immune checkpoint molecules: signaling pathways and implications for cancer immunotherapy. Clin. Cancer Res., 2013, 19(18), 4917-4924.
[170]
Okazaki, T.; Chikuma, S.; Iwai, Y.; Fagarasan, S.; Honjo, T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat. Immunol., 2013, 14(12), 1212-1218.
[171]
Menzies, A.M.; Long, G.V. Systemic treatment for BRAF-mutant melanoma: where do we go next? Lancet Oncol., 2014, 15(9), e371-e381.
[172]
Wolchok, J.D.; Kluger, H.; Callahan, M.K.; Postow, M.A.; Rizvi, N.A.; Lesokhin, A.M.; Segal, N.H.; Ariyan, C.E.; Gordon, R.A.; Reed, K.; Burke, M.M.; Caldwell, A.; Kronenberg, S.A.; Agunwamba, B.U.; Zhang, X.; Lowy, I.; Inzunza, H.D.; Feely, W.; Horak, C.E.; Hong, Q.; Korman, A.J.; Wigginton, J.M.; Gupta, A.; Sznol, M. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med., 2013, 369(2), 122-133.
[173]
Sznol, M. Survival, response duration, and activity by BRAF mutation
(MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558,
ONO-4538) and ipilimumab (IPI) concurrent therapy in ad-vanced
melanoma (MEL). ASCO Annual Meeting Proceedings, 2014.
[174]
Postow, M.A.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.; McDermott, D.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; Shaheen, M.; Ernstoff, M.S.; Minor, D.; Salama, A.K.; Taylor, M.; Ott, P.A.; Rollin, L.M.; Horak, C.; Gagnier, P.; Wolchok, J.D.; Hodi, F.S. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med., 2015, 372(21), 2006-2017.
[175]
Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; Ferrucci, P.F.; Hill, A.; Wagstaff, J.; Carlino, M.S.; Haanen, J.B.; Maio, M.; Marquez-Rodas, I.; McArthur, G.A.; Ascierto, P.A.; Long, G.V.; Callahan, M.K.; Postow, M.A.; Grossmann, K.; Sznol, M.; Dreno, B.; Bastholt, L.; Yang, A.; Rollin, L.M.; Horak, C.; Hodi, F.S.; Wolchok, J.D. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med., 2015, 373(1), 23-34.
Related Books
Frontiers in Clinical Drug Research - Anti-Cancer Agents
NEOPLASIA and FERTILITY
Breast Cancer: Current Trends in Molecular Research
The Evolution of Radionanotargeting towards Clinical Precision Oncology: A Festschrift in Honor of Kalevi Kairemo
Nanotherapeutics for the Treatment of Hepatocellular Carcinoma
Topics in Anti-Cancer Research
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Modern Cancer Therapies and Traditional Medicine: An Integrative Approach to Combat Cancers
Herbal Medicine: Back to the Future
Thrombosis in Cancer: A Medical Professional's Guide to Cancer Associated Thrombosis
Article Metrics
59
4