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Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K.
Villanueva J, Vultur A, 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, Brown KD, Laquerre S, McArthur GA, Sosman JA, Nathanson KL, Herlyn M. Villanueva J, et al. Cancer Cell. 2010 Dec 14;18(6):683-95. doi: 10.1016/j.ccr.2010.11.023. Cancer Cell. 2010. PMID: 21156289 Free PMC article.
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma.
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, Nolop K. Bollag G, et al. Nature. 2010 Sep 30;467(7315):596-9. doi: 10.1038/nature09454. Nature. 2010. PMID: 20823850 Free PMC article. Clinical Trial.
Active Notch1 confers a transformed phenotype to primary human melanocytes.
Pinnix CC, Lee JT, Liu ZJ, McDaid R, Balint K, Beverly LJ, Brafford PA, Xiao M, Himes B, Zabierowski SE, Yashiro-Ohtani Y, Nathanson KL, Bengston A, Pollock PM, Weeraratna AT, Nickoloff BJ, Pear WS, Capobianco AJ, Herlyn M. Pinnix CC, et al. Cancer Res. 2009 Jul 1;69(13):5312-20. doi: 10.1158/0008-5472.CAN-08-3767. Epub 2009 Jun 23. Cancer Res. 2009. PMID: 19549918 Free PMC article.