Article
Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF/MEK cotargeting but result in melanoma drug addiction.
Cancer cell - 9 Feb 2015
Moriceau Gatien, Hugo Willy, Hong Aayoung, Shi Hubing, Kong Xiangju, Yu Clarissa C, Koya Richard C, Samatar Ahmed A, Khanlou Negar, Braun Jonathan, Ruchalski Kathleen, Seifert Heike, Larkin James, Dahlman Kimberly B, Johnson Douglas B, Algazi Alain, Sosman Jeffrey A, Ribas Antoni, Lo Roger S
Abstract excerpt
Combined BRAF- and MEK-targeted therapy improves upon BRAF inhibitor (BRAFi) therapy but is still beset by acquired resistance. We show that melanomas acquire resistance to combined BRAF and MEK inhibition by augmenting or combining mechanisms of single-agent BRAFi resistance. These double-drug resistance-associated genetic configurations significantly altered molecular interactions underlying MAPK pathway...
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