Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.

Major limitations of current melanoma treatments are for instances of relapse and the lack of therapeutic options for BRAF wild-type patients who do not respond to immunotherapy. Many studies therefore focus on killing resistant subpopulations, such as Melanoma Initiating Cells (MICs) to prevent relapse. Here we examined whether combining a GSI (γ-Secretase Inhibitor) with ABT-737 (a small molecule BCL-2/BCL-XL/BCL-W inhibitor) can kill both the non-MICs (bulk of melanoma) and MICs.

Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk and Kill Cancer Stem Cells.

For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30-90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer treatments, and how this approach can be applied as an alternative option to combat melanoma, and overcome melanoma relapse or resistance in current treatment regimens.