Simbulan-Rosenthal CM, et al. - Given the putative value of CD133 as a cancer stem cell marker for different cancers, associated with decreased survival, researchers investigated resistance to MAPK inhibitors in CD133(+) and CD133(-) melanoma cells derived from patients. Exposure to increasing concentrations of trametinib and/or dabrafenib of human melanoma cells was done, either before or after separation into CD133(+) and CD133(-) subpopulations. Following high-dose drug treatment, they noted significant increase in the percentages of CD133(+) cells among parental CD133-mixed lines. In addition, significantly greater IC50s were noted in presorted CD133(+) cells for single and combination MAPKI treatment. As per siRNA knockdown, CD133 and drug resistance have a causal relationship. Microarray and qRT-PCR analyses revealed significant upregulation of ten of 18 ABC transporter genes in the CD133(+) subpopulation, while inhibition of ABC activity was noted to increase sensitivity, suggesting a mechanism for increased drug resistance of CD133(+) cells.