Beyond ABC: Another Mechanism of Drug Resistance in Melanoma Side Population

It has been shown that a side population (SP), which is characterized by high chemical efflux capacity, is present in human melanoma cell lines. However, it was not clear whether patients' samples contain the same subpopulation. In this issue, Luo et al. (2012) report that they have isolated SP cells directly from patients' melanomas. SP cells are resistant to paclitaxel because of the upregulation of ABCB1 and ABCB5. Notably, these cells are also resistant to temozolomide, which is not a substrate for ATP-Binding Cassette (ABC) transporters, in an interleukin (IL)-8-dependent manner. This study provides novel clues for understanding how a small, but critical, subpopulation within melanomas is resistant to therapies.