Involvement of the BH3-only pro-apoptotic BIK/NBK in BRAF/MEK inhibitor induced apoptosis in melanoma cell lines

In patients with BRAF-mutated melanoma specific inhibitors of BRAFV600E and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAFV600E-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells).

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