ESR1 and breast carcinoma: Clinical proof of concept for heterobifunctional degraders has been limited to a small number of oncology programs where compounds targeting estrogen receptor (ARV-471) (refs. 51,52), androgen receptor (ARV-110) (ref. 53) or Bruton’s tyrosine kinase (NX-2127) (ref. 54) have demonstrated, in meeting presentations, varying degrees of target knockdown as well as anti-tumor activity with acceptable safety in phase 1 and phase 2 trials in breast cancer, prostate cancer and lymphoma, respectively.