bortezomib + tamoxifen

Bortezomib + tamoxifen is an investigational combination therapy consisting of bortezomib, a proteasome inhibitor, and tamoxifen, a selective estrogen receptor modulator (SERM). Bortezomib inhibits the 26S proteasome, leading to disruption of multiple signaling cascades including NF-κB pathway inhibition. Tamoxifen acts primarily as an antagonist of the estrogen receptor in breast tissue. The rationale for combining these agents is based on preclinical evidence that bortezomib can enhance tamoxifen-induced apoptosis by inhibiting NF-κB signaling and potentially overcoming resistance to hormonal therapy. This combination has been studied in phase II clinical trials for recurrent malignant gliomas and metastatic breast cancer resistant to endocrine therapy; however, clinical benefit has been limited[1][2][9].