A Novel Resistance Mechanism To Plx4032 In The Human Melanoma Cell Line Mel-Xy3 Involves Acquisition Of Stem Cell-Like Characteristics

Activating BRAF mutations, in particular V600E, occurs in approximately 50% of cutaneous melanomas. PLX4032 (vemurafenib), an ATP-competitive BRAF inhibitor, displays remarkable activity, leading to an increase in progression-free and overall survival in patients with BRAF V600E mutated melanoma, pointing to a strong dependence of this tumor on the MAP kinase pathway. However, patients treated with this drug almost invariably recur, and several resistance mechanisms have already been described. In this work, we have investigated the effects of long-term treatment (5 weeks - 5 months) with PLX4032 in the human melanoma cell line MEL-XY3. The sensitivity of the heterozygous, BRAF mutated (V600E) parental MEL-XY3 cells (XY3 wt) to PLX4032 was investigated, and the IC50 was Citation Format: Florencia Madorsky, Antonela Baron, Jose Mordoh. A novel resistance mechanism to PLX4032 in the human melanoma cell line MEL-XY3 involves acquisition of stem cell-like characteristics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 692. doi:10.1158/1538-7445.AM2014-692