fulvestrant + ixazomib

Fulvestrant + ixazomib is an investigational drug combination studied primarily in patients with advanced, estrogen receptor-positive (ER+) breast cancer that has become resistant to fulvestrant monotherapy. Fulvestrant is a selective estrogen receptor downregulator and pure antiestrogen that blocks ER transcriptional activity and induces degradation of ER alpha, thereby inhibiting tumor growth driven by the ER pathway. Ixazomib is an oral small molecule proteasome inhibitor that disrupts protein homeostasis in cancer cells, leading to apoptosis. Preclinical studies suggest proteasome inhibitors like ixazomib can enhance the effects of fulvestrant by increasing accumulation of insoluble ER and activating unfolded protein response pathways. In a phase Ib clinical trial, this combination showed a favorable safety profile and preliminary antitumor activity in patients with advanced or metastatic ER+ breast cancer progressing on prior fulvestrant therapy[1][2].