Genes expression alterations associated with resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improves the outcome of patients with advanced estrogen receptor-positive (ER+) breast cancer. However, resistance to this treatment and resultant disease progression remains a major clinical challenge. High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored. To identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed global gene expression analysis and RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. Overall design: Cells sensitive, resistant to fulvestrant or resistant to combined fulvestrant and CDK4/6i derived from MCF7 and T47D cell lines were included in the study. Cells were grown to reach 70-80% confluency and RNA was extracted using TRIzol™ Reagent according to manufacturer's instructions