Kinase Plasticity in Response to Vandetanib Enhances Sensitivity to Tamoxifen and Identifies Co-Treatment Strategies in Estrogen Receptor Positive Breast Cancer

We study the effect of vandetanib treatment in enhancing sensitivity to ET in ET-sensitive and -resistant ER+ breast cancer models. Vandetanib treatment alters the gene expression program of ER+ breast cancer cells resulting in a less proliferative and more estrogen responsive Luminal-A like character. These results support future investigation to determine optimal targeting strategies of reprogrammed networks, such as activating HER2 expression, in patients with ET resistant ER+ breast cancer. This study comprises single cell RNA sequencing of ER+ breast cancer patient-derived samples treated ex vivo with vandetanib, tamoxifen and vehicle, and bulk rna sequencing of MCF7 and T47D cell lines (ER+ human breast cancer cell lines) with the same treatments.