Having validated the clinical relevance of PDE4D as an attractive therapeutic target in SOC-resistant ER+ breast cancer, we then developed tamoxifen, fulvestrant and palbociclib-resistant derivatives of MCF-7 and T47D cells by long-term drug treatment over 9 months (Supplementary Fig. 6a–c) to examine the mechanistic roles of PDE4D in SOC resistance. The gene discussed is PDE4D; the disease is breast cancer.