bortezomib + fulvestrant

Bortezomib + fulvestrant is an investigational combination therapy evaluated for the treatment of hormone receptor-positive, estrogen receptor (ER)-positive metastatic breast cancer resistant to aromatase inhibitors. Bortezomib is a small molecule proteasome inhibitor that prevents the degradation of proteins within cells, while fulvestrant is a selective estrogen receptor degrader (SERD) that binds to and accelerates the degradation of ER, leading to downregulation of ER signaling. Preclinical studies demonstrated synergistic antitumor activity when combining these agents; bortezomib enhances accumulation of cytoplasmic ER aggregates induced by fulvestrant, promoting a proapoptotic unfolded protein response and cell death. In phase II clinical trials, this combination delayed disease progression compared with fulvestrant alone and showed potential in overcoming or delaying resistance to endocrine therapy[1][2][3][5].