Itors with clinically obtainable agents for further evaluation. On the list of appropriate situations for such a regime is within the case ofsubmit your manuscript | dovepressDrug Style, Improvement and Therapy 2014:DovepressDovepressinsulin in drug resistance of melanoma 14. Bollag G, Tsai J, Zhang J, et al. Vemurafenib: the initial drug approved for BRAF-mutant cancer. Nat Rev Drug Discov. 2012;11(11):873?86. 15. Nikolaou VA, Stratigos AJ, Flaherty KT, Tsao H. Melanoma: new insights and new therapies. J Invest Dermatol. 2012;132(3 Pt 2): 854?63. 16. Smalley KS, Sondak VK. Melanoma ?an unlikely poster kid for customized cancer therapy. N Engl J Med. 2010;363(9):876?78. 17. Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature. 2010;468(7326):973?77. 18. Johannessen CM, Boehm JS, Kim SY, et al. COT drives resistance to RAF inhibition by way of MAP kinase pathway reactivation. Nature. 2010;468(7326):968?72. 19. Poulikakos PI, Persaud Y, Janakiraman M, et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature. 2011;480(7377):387?90. 20. Shi H, Moriceau G, Kong X, et al. Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun. 2012;three:724. 21. Emery CM, Vijayendran KG, Zipser MC, et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009;106(48):20411?0416. 22. Paraiso KH, Xiang Y, Rebecca VW, et al. PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res. 2011;71(7):2750?760. 23. Villanueva J, Vultur A, Lee JT, et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma might be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010;18(6): 683?95. 24. Jiang CC, Lai F, Thorne RF, et al. MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720. Clin Cancer Res. 2011;17(4): 721?30. 25. Madonna G, Ullman CD, Gentilcore G, Palmieri G, Ascierto PA. NF-B as potential target in the treatment of melanoma. J Transl Med. 2012;10:53. 26. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.1471260-52-2 Purity N Engl J Med.1-Bromo-2-chloro-4,5-difluorobenzene web 2012;367(18):1694?703.PMID:22664133 27. Falchook GS, Lewis KD, Infante JR, et al. Activity of the oral MEK inhibitor trametinib in patients with sophisticated melanoma: a phase 1 dose-escalation trial. Lancet Oncol. 2012;13(8):782?89. 28. Infante JR, Fecher LA, Falchook GS, et al. Security, pharmacokinetic, pharmacodynamic, and efficacy information for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol. 2012;13(8): 773?81. 29. Shimizu T, Tolcher AW, Papadopoulos KP, et al. The clinical effect of the dual-targeting technique involving PI3K/AKT/mTOR and RAS/ MEK/ERK pathways in individuals with advanced cancer. Clin Cancer Res. 2012;18(eight):2316?325. 30. Pollak M. The insulin and insulin-like growth issue receptor family members in neoplasia: an update. Nat Rev Cancer. 2012;12(three):159?69. 31. Pollak M. The insulin receptor/insulin-like growth issue receptor household as a therapeutic target in oncology. Clin Cancer Res. 2012;18(1): 40?0. 32. Chen J, Katsifis A, Hu C, Huang XF. Insulin decreases therapeutic efficacy in colon cancer cell line HT29 through the activation on the PI3K/ Akt pathway. Curr Drug Discov Technol. 2011;8(two):119?25.