Emerging targeted therapies for melanoma treatment (Review)
- Authors:
- Angela Russo
- Bartolomea Ficili
- Saverio Candido
- Franca Maria Pezzino
- Claudio Guarneri
- Antonio Biondi
- Salvatore Travali
- James A. McCubrey
- Demetrios A. Spandidos
- Massimo Libra
-
Affiliations: Laboratory of Translational Oncology and Functional Genomics, Section of General Pathology and Oncology, Department of Biomedical Sciences, University of Catania, I-95124 Catania, Italy, Department of Social Territorial Medicine, Section of Dermatology, University of Messina, I-98125 Messina, Italy, Department of Surgery, University of Catania, I-95124 Catania, Italy, Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA, Department of Virology, Medical School, University of Crete, Heraklion 71003, Crete, Greece - Published online on: June 3, 2014 https://doi.org/10.3892/ijo.2014.2481
- Pages: 516-524
-
Copyright: © Russo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
This article is mentioned in:
Abstract
 |
|
Bataille V, Winnett A, Sasieni P, Newton Bishop JA and Cuzick J: Exposure to the sun and sunbeds and the risk of cutaneous melanoma in the UK: a case-control study. Eur J Cancer. 40:429–435. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DS, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA and Chin L: A landscape of driver mutations in melanoma. Cell. 150:251–263. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Thomas NE, Berwick M and Cordeiro-Stone M: Could BRAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet radiation? J Invest Dermatol. 126:1693–1696. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Thomas NE, Edmiston SN, Alexander A, Millikan RC, Groben PA, Hao H, Tolbert D, Berwick M, Busam K, Begg CB, Mattingly D, Ollila DW, Tse CK, Hummer A, Lee-Taylor J and Conway K: Number of nevi and early-life ambient UV exposure are associated with BRAF-mutant melanoma. Cancer Epidemiol Biomarkers Prev. 16:991–997. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Venesio T, Chiorino G, Balsamo A, Zaccagna A, Petti C, Scatolini M, Pisacane A, Sarotto I, Picciotto F and Risio M: In melanocytic lesions the fraction of BRAFV600Ealleles is associated with sun exposure but unrelated to ERK phosphorylation. Mod Pathol. 21:716–726. 2008.PubMed/NCBI | |
|
Candido S, Rapisarda V, Marconi A, Malaponte G, Bevelacqua V, Gangemi P, Scalisi A, McCubrey JA, Maestro R, Spandidos DA, Fenga C and Libra M: Analysis of the B-RAFV600Emutation in cutaneous melanoma patients with occupational sun exposure. Oncol Rep. 31:1079–1082. 2014. | |
|
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, 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 BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA: Mutations of the BRAF gene in human cancer. Nature. 417:949–954. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Libra M, Malaponte G, Navolanic PM, Gangemi P, Bevelacqua V, Proietti L, Bruni B, Stivala F, Mazzarino MC, Travali S and McCubrey JA: Analysis of BRAF mutation in primary and metastatic melanoma. Cell Cycle. 4:1382–1384. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Garnett MJ and Marais R: Guilty as charged: B-RAF is a human oncogene. Cancer Cell. 6:313–319. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Ascierto PA, Kirkwood JM, Grob J, Simeone E, Grimaldi AM, Maio M, Palmieri G, Testori A, Marincola FM and Mozzillo N: The role of BRAF V600 mutation in melanoma. J Transl Med. 10:852012. View Article : Google Scholar : PubMed/NCBI | |
|
Chen B, Tardell C, Higgins B, Packman K, Boylan JF and Niu H: BRAFV600E negatively regulates the AKT pathway in melanoma cell lines. PLoS One. 7:e425982012. View Article : Google Scholar : PubMed/NCBI | |
|
Vredeveld LC, Possik PA, Smit MA, Meissl K, Michaloglou C, Horlings HM, Ajouaou A, Kortman PC, Dankort D, McMahon M, Mooi WJ and Peeper DS: Abrogation of BRAFV600E-induced senescence by PI3K pathway activation contributes to melanomagenesis. Genes Dev. 26:1055–1069. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Lipkin G: Plasticity of the cancer cell: implications for epigenetic control of melanoma and other malignancies. J Invest Dermatol. 128:2152–2155. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Villanueva J, Adina V, Lee JT, Somasundaram R, Fukunaga-Kalabis M, Cipolla AK, Wubbenhorst B, Xu X, Gimotty PA, Kee D, Santiago-Walker AE, Letrero R, D’Andrea K, Pushparajan A, Hayden JE, Kimberly BD, Laquerre S, McArthur GA, Sosman JA, Nathanson KL and Herlyn M: Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by co-targeting MEK and IGF-1R/PI3K. Cancer Cell. 18:683–695. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Viola JR, Rafael DF, Wagner E, Besch R and Hindawi MO: Gene therapy for advanced melanoma: selective targeting and therapeutic nucleic acids. J Drug Deliv. 2013:8973482013. View Article : Google Scholar : PubMed/NCBI | |
|
Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM and Lynch M: Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 7:3129–3140. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Karasarides M, Chiloeches A, Hayward R, Niculescu-Duvaz D, Scanlon I, Friedlos F, Ogilvie L, Hedley D, Martin J, Marshall CJ, Springer CJ and Marais R: B-RAF is a therapeutic target in melanoma. Oncogene. 23:6292–6298. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley BL, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G and Trail PA: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Strumberg D, Awada A, Piccart P, Hirte H, Moore M, Clark J, Lenz HJ, Lathia C, Schwartz B and Humphrey R: Final report of the phase I clinical program of the novel raf kinase inhibitor BAY 43-9006 in patients with refractory solid tumors. J Clin Oncol. 22:2032003. | |
|
Strumberg D: Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today. 41:773–784. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D, Strumberg D, Brendel E, Haase CG, Schwartz B and Piccart M: Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer. 92:1855–1861. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, Gibbens I, Hackett S, James M, Schuchter LM, Nathanson KL, Xia C, Simantov R, Schwartz B, Poulin-Costello M, O’Dwyer PJ and Ratain MJ: Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer. 95:581–586. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Chakraborty R, Wieland CN and Comfere N: Molecular targeted therapies in metastatic melanoma. Pharmgenomics Pers Med. 6:49–56. 2013.PubMed/NCBI | |
|
McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, Nicoletti F, Fagone P, Malaponte G, Mazzarino MC, Candido S, Libra M, Bäsecke J, Mijatovic S, Maksimovic-Ivanic D, Milella M, Tafuri A, Cocco L, Evangelisti C, Chiarini F and Martelli AM: Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 3:954–987. 2012.PubMed/NCBI | |
|
McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, Mazzarino MC, Fagone P, Nicoletti F, Bäsecke J, Mijatovic S, Maksimovic-Ivanic D, Milella M, Tafuri A, Chiarini F, Evangelisti C, Cocco L and Martelli AM: Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 3:1068–1111. 2012.PubMed/NCBI | |
|
Pecuchet N, Lebbe C, Mir O, Billemont B, Blanchet B, Franck N, Viguier M, Coriat R, Tod M, Avril MF and Goldwasser F: Sorafenib in advanced melanoma: a critical role for pharmacokinetics? Br J Cancer. 107:455–461. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Eisen T, Marais R, Affolter A, Lorigan P, Robert C, Corrie P, Ottensmeier C, Chevreau C, Chao D, Nathan PD, Jouary T, Harries M, Negrier S, Montegriffo E, Ahmad T, Gibbens I, James MG, Strauss UP, Prendergast S and Gore ME: Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer. 105:353–359. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M and Bollag G: Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc Natl Acad Sci USA. 105:3041–3046. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Jang S and Atkins MB: Which drug, and when, for patients with BRAF-mutant melanoma? Lancet Oncol. 14:60–69. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
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 and McArthur GA: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 364:2507–2516. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Joseph EW, Pratilas CA, Poulikakos PI, Tadi M, Wang W, Taylor BS, Halilovic E, Persaud Y, Xing F, Viale A, Tsai J, Chapman PB, Bollag G, Solit DB and Rosen N: The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner. Proc Natl Acad Sci USA. 107:14903–14908. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, Burton EA, Wong B, Tsang G, West BL, Powell B, Shellooe R, Marimuthu A, Nguyen H, Zhang KY, Artis DR, Schlessinger J, Su F, Higgins B, Iyer R, D’Andrea K, Koehler A, Stumm M, Lin PS, Lee RJ, Grippo J, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, Chapman PB, Flaherty KT, Xu X, Nathanson KL and Nolop K: Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 467:596–599. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK and Ribas A: Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 366:707–714. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Oberholzer PA, Kee D, Dziunycz P, Sucker A, Kamsukom N, Jones R, Roden C, Chalk CJ, Ardlie K, Palescandolo E, Piris A, MacConaill LE, Robert C, Hofbauer GF, McArthur GA, Schadendorf D and Garraway LA: RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. J Clin Oncol. 30:316–321. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A and Marais R: RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 366:207–215. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K and Chapman PB: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 363:809–819. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Corcoran RB, Settleman J and Engelman JA: Potential therapeutic strategies to overcome acquired resistance to BRAF or MEK inhibitors in BRAF mutant cancers. Oncotarget. 2:336–346. 2011.PubMed/NCBI | |
|
McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Basecke J, Maksimovic-Ivanic D, Mijatovic S, Montalto G, Cervello M, Cocco L and Martelli AM: Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 226:2762–2781. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Shao Y and Aplin AE: Akt3-mediated resistance to apoptosis in B-RAF-targeted melanoma cells. Cancer Res. 70:6670–6681. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Emery CM, Vijayendrana KG, Zipserc MC, Sawyera AM, Niua L, Kima JJ, Hattona C, Choprad R, Oberholzera PA, Karpovac MB, MacConailla LE, Zhangf J, Grayf NS, Sellersd WR, Dummerc R and Garrawaya LA: MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA. 106:20411–20416. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Greger JG, Eastman SD, Zhang V, Bleam MR, Hughes AM, Smitheman KN, Dickerson SH, Laquerre SG, Liu L and Gilmer TM: Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 11:909–920. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Aplin AE, Kaplan FM and Shao Y: Mechanisms of resistance to RAF inhibitors in melanoma. J Invest Dermatol. 131:1817–1820. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Trunzer K, Pavlick AC, Schuchter L, Gonzalez R, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Kim KB, Weber JS, Hersey P, Long GV, Lawrence D, Ott PA, Amaravadi RK, Lewis KD, Puzanov I, Lo Roger S, Koehler A, Kockx M, Spleiss O, Schell-Steven A, Gilbert HN, Cockey L, Bollag G, Lee RJ, Joe AK, Sosman JA and Ribas A: Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol. 31:1767–1774. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Hauschild A, Grob J, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martín-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin A, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V and Chapman PB: Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 380:358–365. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin A, Guckert M, Goodman V, Streit M, Kirkwood JM and 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. 13:1087–1095. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Ascierto PA, Minor D, Ribas A, Lebbe C, O’Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob J, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin A, Mazumdar J, Goodman VL and Trefzer U: Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 31:3205–3211. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, Hamid O, Infante JR, Millward M, Pavlick AC, O’Day SJ, Blackman SC, Curtis CM, Lebowitz P, Ma B, Ouellet D and Kefford RF: Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 379:1893–1901. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Trefzer U, Minor D, Ribas A, Lebbe C, Siegfried A, Arya N, Guckert M, Schadendorf D, Kefford R, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim K, Goodman V and Ascierto PA: BREAK-2: a Phase IIA trial of the selective BRAF kinase inhibitor GSK2118436 in patients with BRAF mutation-positive (V600E/K) metastatic melanoma. Pigm Cell Melanoma R. 24:10202011. | |
|
Gray-Schopfer V, Wellbrock C and Marais R: Melanoma biology and new targeted therapy. Nature. 445:851–857. 2007. View Article : Google Scholar | |
|
Johnson DB and Sosman JA: Update on the targeted therapy of melanoma. Curr Treat Options Oncol. 14:280–292. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Thompson N and Lyons J: Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer drug discovery. Curr Opin Pharmacol. 5:350–356. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Catalanotti F, Solit DB, Pulitzer MP, Berger MF, Scott SN, Iyriboz T, Lacouture ME, Panageas KS, Wolchok JD, Carvajal RD, Schwartz GK, Rosen N and Chapman PB: Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma. Clin Cancer Res. 19:2257–2264. 2013. View Article : Google Scholar | |
|
Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JM, Utikal J, Dreno B, Nyakas M, Middleton MR, Becker JC, Casey M, Sherman LJ, Wu FS, Ouellet D, Martin AM, Patel K and Schadendorf D: Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 367:107–114. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Byron SA, Loch DC, Wellens CL, Wortmann A, Wu J, Wang J, Nomoto K and Pollock PM: Sensitivity to the MEK inhibitor E6201 in melanoma cells is associated with mutant BRAF and wildtype PTEN status. Mol Cancer. 11:752012. View Article : Google Scholar : PubMed/NCBI | |
|
Falchook GS, Lewis KD, Infante JR, Gordon MS, Vogelzang NJ, De Marini DJ, Sun P, Moy C, Szabo SA, Roadcap LT, Peddareddigari VG, Lebowitz PF, Le NT, Burris HA III, Messersmith WA, O’Dwyer PJ, Kim KB, Flaherty K, Bendell JC, Gonzalez R, Kurzrock R and Fecher LA: Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 13:782–789. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Yamaguchi T, Kakefuda R, Tajima N, Sowa Y and Sakai T: Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol. 39:23–31. 2011.PubMed/NCBI | |
|
Gilmartin AG, Bleam MR, Groy A, Moss KG, Minthorn EA, Kulkarni SG, Rominger CM, Erskine S, Fisher KE, Yang J, Zappacosta F, Annan R, Sutton D and Laquerre SG: GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 17:989–1000. 2011. View Article : Google Scholar | |
|
Akinleye A, Furqan M, Mukhi N, Ravella P and Liu D: MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 6:272013. View Article : Google Scholar : PubMed/NCBI | |
|
Robert C, Flaherty KT, Hersey P, Nathan P, Garbe C, Milhem MM, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JMG, Utikal J, Casey M, Sherman LJ, Crist WA, Wu FS, Patel K and Schadendorf D: METRIC phase III study: efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAF V600E/K mutant advanced or metastatic melanoma (MM). J Clin Oncol. 30(Suppl): abs. LBA8509. 2012. | |
|
Klinac D, Gray ES, Millward M and Ziman M: Advances in personalized targeted treatment of metastatic melanoma and non-invasive tumor monitoring. Front Oncol. 3:542013. View Article : Google Scholar : PubMed/NCBI | |
|
Kim KB, Lewis K, Pavlick A, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P, Gonzalez R, Ott PA, Long G, Gardner OS, Ouellet D, Xu Y, De Marini DJ, Le N, Patel K and Kefford R: A phase II study of the MEK1/MEK2 inhibitor GSK1120212 in metastatic BRAF-V600E or K mutant cutaneous melanoma patients previously treated with or without a BRAF inhibitor. International Melanoma Congress. Pigment Cell Res. 24:990–1075. 2011. | |
|
Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, Ohta M, Jazag A, Guleng B, Tateishi K, Asaoka Y, Matsumura M, Kawabe T and Omata M: Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res. 65:4562–4567. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Isakoff SJ, Engelman JA, Irie HY, Luo J, Brachmann SM, Pearline RV, Cantley LC and Brugge JS: Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res. 65:10992–11000. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao JJ, Liu Z, Wang L, Shin E, Loda MF and Roberts TM: The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci USA. 102:18443–18448. 2005. View Article : Google Scholar | |
|
Janku F, Wheler JJ, Naing A, Stepanek VM, Falchook GS, Fu S, Garrido-Laguna I, Tsimberidou AM, Piha-Paul SA, Moulder SL, Lee JJ, Luthra R, David SH and Kurzrock R: PIK3CA mutations in advanced cancers: characteristics and outcomes. Oncotarget. 3:1566–1575. 2012.PubMed/NCBI | |
|
Zhao L and Vogt PK: Class I PI3K in oncogenic cellular transformation. Oncogene. 27:5486–5496. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Ligresti G, Militello L, Steelman LS, Cavallaro A, Basile F, Nicoletti F, Stivala F, McCubrey JA and Libra M: PIK3CA mutations in human solid tumors. Role in sensitivity to various therapeutic approaches. Cell Cycle. 8:1352–1358. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Hafsi S, Pezzino FM, Candido S, Ligresti G, Spandidos DA, Soua Z, McCubrey JA, Travali S and Libra M: Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance. Int J Oncol. 40:639–644. 2011.PubMed/NCBI | |
|
Mendoza MC, Er EE and Blenis J: The Ras-ERK and PI3KmTOR pathways: cross-talk and compensation. Trends Biochem Sci. 36:320–328. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L and Robertson GP: Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64:7002–7010. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Meier F, Schittek B, Busch S, Garbe C, Smalley K, Satyamoorthy K, Li G and Herlyn M: The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma. Front Biosci. 10:2986–3001. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Russo AE, Torrisi E, Bevelacqua Y, Perrotta R, Libra M, McCubrey JA, Spandidos DA, Stivala F and Malaponte G: Melanoma: molecular pathogenesis and emerging target therapies (Review). Int J Oncol. 34:1481–1489. 2009.PubMed/NCBI | |
|
Brana I and Siu LL: Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment. BMC Med. 10:1612012. View Article : Google Scholar : PubMed/NCBI | |
|
Ogita S and Lorusso P: Targeting phosphatidylinositol 3 kinase (PI3K)-Akt beyond rapalogs. Target Oncol. 6:103–117. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Huang A, Fritsch C, Wilson C, Reddy A, Liu M, Lehar J, Quadt C, Hofmann F and Schlegel R: Single agent activity of PIK3CA inhibitor BYL719 in a broad cancer cell line panel. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; Chicago, IL, Philadelphia, PA. Am Assoc Cancer Res. abs. 3749. 2012 | |
|
Jessen K, Kessler L, Kucharski J, Guo X, Staunton J, Janes M, Elia M, Banerjee U, Lan L, Wang S, Stewart J, Luzader A, Darjania L, Li L, Chan K, Martin M, Ren P, Rommel C and Liu Y: A potent and selective PI3K inhibitor, INK1117, targets human cancers harboring oncogenic PIK3CA mutations. In: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; San Francisco, CA, Philadelphia, PA. Am Assoc Cancer Res. 10. abs. A171. 2011 | |
|
Britten CD: PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol. 71:1395–1409. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Liu P, Cheng H, Roberts TM and Zhao JJ: Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 8:627–644. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Markman B, Dienstmann R and Tabernero J: Targeting the PI3K/Akt/mTOR pathway - beyond rapalogs. Oncotarget. 1:530–543. 2010.PubMed/NCBI | |
|
Mansh M: Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. Yale J Biol Med. 84:381–389. 2011.PubMed/NCBI | |
|
Sondak VK, Smalley KS, Kudchadkar R, Grippon S and Kirkpatrick P: Ipilimumab. Nat Rev Drug Discov. 10:411–412. 2011. View Article : Google Scholar | |
|
Fellner C: Ipilimumab (Yervoy) prolongs survival in advanced melanoma. Drug Forecast. 37:503–530. 2012.PubMed/NCBI | |
|
Tjin EP, Konijnenberg D, Krebbers G, Mallo H, Drijfhout JW, Franken KL, van der Horst CM, Bos JD, Nieweg OE, Kroon BB, Haanen JB, Melief CJ, Vyth-Dreese FA and Luiten RM: T cell immune function in tumor, skin, and peripheral blood of advance stage melanoma patients: implications for immunotherapy. Clin Cancer Res. 17:5736–5747. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Levings MK, Sangregorio R and Roncarolo MG: Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med. 193:1295–1302. 2001. | |
|
Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM and Chen L: Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 7:95–106. 2007. View Article : Google Scholar | |
|
Agarwala SS: Current systemic therapy for metastatic melanoma. Expert Rev Anticancer Ther. 9:587–595. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Kirkwood JM, Tarhini AA, Panelli MC, Moschos SJ, Zarour HM, Butterfield LH and Gogas HJ: Next generation of immunotherapy for melanoma. J Clin Oncol. 26:3445–3455. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Antony GK and Dudek AZ: Interleukin 2 in cancer therapy. Curr Med Chem. 17:3297–3302. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Chmielowski B: Ipilimumab: a first-in-class T-cell potentiator for metastatic melanoma. J Skin Cancer. 2013:4238292013. View Article : Google Scholar : PubMed/NCBI | |
|
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, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A and Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 363:211–223. 2010.PubMed/NCBI | |
|
Robert C and Ghiringhelli F: What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist. 14:848–861. 2009.PubMed/NCBI | |
|
Hwu P: Treating cancer by targeting the immune system. N Engl J Med. 363:779–781. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, Waterfield W, Schadendorf D, Smylie M, Guthrie T Jr, Grob JJ, Chesney J, Chin K, Chen K, Hoos A, O’Day SJ and Lebbé C: Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 11:155–164. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Lipson EJ and Drake CG: Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res. 17:6958–6962. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Di Giacomo AM, Calabrò L, Danielli R, Fonsatti E, Bertocci E, Pesce I, Fazio C, Cutaia O, Giannarelli D, Miracco C, Biagioli M, Altomonte M and Maio M: Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme. Cancer Immunol Immunother. 62:1021–1028. 2013.PubMed/NCBI | |
|
Feng Y, Roy A, Masson E, Chen T, Humphrey R and Weber JS: Exposure-response relationships of the efficacy and safety of ipilimumab in patients with advanced melanoma. Clin Cancer Res. 19:3977–3986. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Melero I, Grimaldi AM, Perez-Gracia JL and Ascierto PA: Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clin Cancer Res. 19:997–1008. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM and Sznol M: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Shahabi V, Whitney G, Hamid O, Schmidt H, Chasalow SD, Alaparthy S and Jackson JR: Assessment of association between BRAF-V600E mutation status in melanomas and clinical response to ipilimumab. Cancer Immunol Immunother. 61:733–737. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Davar D, Tarhini AA and Kirkwood JM: Adjuvant immunotherapy of melanoma and development of new approaches using the neoadjuvant approach. Clin Dermatol. 31:237–250. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Lo RS: Combinatorial therapies to overcome B-RAF inhibitor resistance in melanomas. Pharmacogenomics. 13:125–128. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Infante JR, Falchook GS, Lawrence DP, Weber JS, Kefford RF, Bendell JC, Kurzrock R, Shapiro G, Kudchadkar RR, Long GV, Burris HA, Kim KB, Clements A, Peng S, Yi B, Allred AJ, Ouellet D, Patel K, Lebowitz PF and Flaherty KT: Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436). J Clin Oncol. 29(Suppl): abs. CRA8503. 2011. | |
|
Weber JS, Flaherty KT, Infante JR, Falchook GS, Kefford R, Daud A, Hamid O, Gonzalez R, Kudchadkar RR, Lawrence DP, Burris HA, Long GV, Algazi AP, Lewis KD, Kim KB, Puzanov I, Sun P, Little SM, Patel K and Sosman JA: Updated safety and efficacy results from a phase I/II study of the oral BRAF inhibitor dabrafenib (GSK2118436) combined with the oral MEK 1/2 inhibitor trametinib (GSK1120212) in patients with BRAFi-naïve metastatic melanoma. J Clin Oncol. 30(Suppl): abs. 8510. 2012. | |
|
Curti BD and Urba WJ: Integrating new therapies in the treatment of advanced melanoma. PhD Current Treatment Options in Oncology. Skin Cancer. 13:327–339. 2012.PubMed/NCBI | |
|
Ascierto PA, Simeone E, Giannarelli D, Grimaldi AM, Romano A and Mozzillo N: Sequencing of BRAF inhibitors and ipilimumab in patients with metastatic melanoma: a possible algorithm for clinical use. J Transl Med. 10:1072012. View Article : Google Scholar : PubMed/NCBI | |
|
Comin-Anduix B, Chodon T, Sazegar H, Matsunaga D, Mock S, Jalil J, Escuin-Ordinas H, Chmielowski B, Koya RC and 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. 16:6040–6048. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wargo JA, Cogdill A, Dang P, Gupta R, Piris A, Boni A, Garber HR, Ott H, Newton LP, Flaherty KT, Lawrence DP, Tsao H and Fisher DE: Treatment with a selective inhibitor of BRAFV600E increases melanocyte antigen expression and CD8 T cell infiltrate in tumors of patients with metastatic melanoma. Cancer Res. 71:abs. 95. 2011. View Article : Google Scholar | |
|
Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P and Scolyer RA: Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 18:1386–1394. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Mijatovic S, Maksimovic-Ivanica D, Mojic M, Malaponte G, Libra M, Cardile V, Miljkovic D, Harhaji L, Dabideen D, Cheng KF, Bevelacqua Y, Donia M, Garotta G, Al-Abed Y, Stosic-Grujicic S and Nicoletti F: Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells. Nitric Oxide. 19:177–183. 2008. View Article : Google Scholar | |
|
Donia M, Mangano K, Fagone P, De Pasquale R, Dinotta F, Coco M, Padron J, Al-Abed Y, Lombardo GA, Maksimovic-Ivanic D, Mijatovic S, Zocca M, Perciavalle V, Stosic-Grujicic S and Nicoletti F: Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells. Oncol Rep. 28:682–688. 2012.PubMed/NCBI |
