The potential for these molecules to have therapeutic potential was appreciated in 2019, with the entry of two first-in-human (FIH) trials: the PROTACs ARV-110 and ARV-471, targeting the AR in heavily pretreated patients with metastatic, castration resistance prostate cancer, and estrogen receptor (ER) in patients with ER-positive breast cancer, respectively [29,30]. Here, ESR1 is linked to breast cancer.