To test the role of PDE4D targeting to overcome SOC resistance in a more clinically relevant setup, we examined the expression of PDE4D in an in vivo-derived tamoxifen-resistant ER+ PDX, HBCx22 TamR as well as in three different PDX models collected from endocrine resistant, metastatic ER+ breast cancer patients (Supplementary Fig. 11a, Supplementary Table 1)36. This evidence concerns the gene ESR1 and breast carcinoma.