Figure 1.

Acquisition of CDK7i resistance in TNBC cells. CDK7 inhibitor–sensitive/parental TNBC cell lines MDA-MB-468 (468) and MDA-MB-231 (231) and resistant MDA-MB-468 (468R) and MDA-MB-231 (231R) cells were treated with either vehicle or the following CDK7 inhibitors at increasing doses: (A) THZ1, (B) THZ2, or (C) SY-1365 for 72 h and the relative cell number was assessed using crystal violet staining. For these experiments, the dose–response curves were significantly different between the sensitive/parental lines compared with the isogenic resistant lines (p < 0.05). D, table of IC₅₀s from the CDK7i dose–response curves. E, sensitive/parental and resistant MDA-MB-468 cells were treated with dimethyl sulfoxide or 50 nM THZ1 for 72 h, whereas MDA-MB-231-sensitive/parental and resistant MDA-MB-231 cells were treated with dimethyl sulfoxide or 75 nM THZ1. All cell lines were then replated and analyzed for colony formation after 8 days of growth in drug-free, complete media. For all experiments, ∗p < 0.05. n = 3 to 4 experiments, each completed in triplicate. Values are means ± SD.