Estrogen receptor (degrader)

Class

novel oral selective estrogen receptor degrader (SERD); binds ER competitively with higher affinity than fulvestrant; developed by Shenzhen Fuwo Pharmaceutical (Forward Pharmaceuticals)

Pathway

degrades/antagonizes ER, with preclinical antitumor activity in both ESR1 wild-type and ESR1-mutant breast cancer models; studied as monotherapy and in combination with palbociclib in ER+/HER2- advanced/metastatic breast cancer, including ESR1-mutated disease

The estrogen receptor (ER) is a nuclear hormone receptor that, when activated by estrogen, turns on genes that drive cell division. In many breast cancers, tumor cells depend on this signal to grow, making ER a longstanding target for treatment. Selective estrogen receptor degraders (SERDs) are small molecules that bind ER and, rather than simply blocking it, trigger its breakdown by the cell's protein-disposal machinery, removing the receptor rather than leaving an inactive version that could still be reactivated. This matters because breast tumors treated with earlier hormonal therapies, particularly aromatase inhibitors, often develop mutations in the ER gene (ESR1) that let the receptor signal without estrogen present; degrading the receptor itself can still suppress this altered signaling. SERDs are studied both alone and alongside drugs that block the cell-cycle machinery further downstream, since combining upstream hormonal blockade with downstream cell-cycle inhibition can more thoroughly halt tumor cell proliferation. This class broadly matters in estrogen-receptor-positive, HER2-negative breast cancer, including disease that has become resistant to prior hormonal treatments through ESR1 mutation, a common clinical challenge in this tumor type.