Triple combination targeting PI3K, ER, and CDK4/6 inhibits growth of ER-positive breast cancer resistant to fulvestrant and CDK4/6 or PI3K inhibitor

[摘要] Despite the improved outcome of advanced estrogenreceptor-positive (ER+) breast cancer patients treated withendocrine therapy in combination with either a cyclindependent kinase 4/6 inhibitor (CDK4/6i) or a phosphoinositide 3-kinase inhibitor (PI3Ki), the disease willeventually progress, and the optimal treatment strategyupon progression remains undefined [1–4]. To addressthis, we developed MCF-7- and T47D-derived PIK3CAmutated breast cancer cell lines [5] resistant to combinedCDK4/6i palbociclib and fulvestrant (MPF-R and TPFR) or combined PI3Ki alpelisib and fulvestrant (MAF-Rand TAF-R), respectively (Supplementary Materials andMethods). Drug-sensitive isogenic cells (M-S and T-S)grown in parallel with MPF-R and TPF-R cells and theoriginal MCF-7/S0.5 and T47D cells were analyzed forcomparison.

[学科分类] 社会科学、人文和艺术（综合）