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Bortezomib (often abbreviated as BTZ) is a proteasome inhibitor that has been approved for the treatment of certain types of cancers, most notably multiple myeloma and mantle cell lymphoma.
Mechanism of Action
Proteasome Inhibition:
Bortezomib targets the 26S proteasome, a complex responsible for degrading ubiquitinated proteins. By inhibiting the proteasome’s activity, bortezomib causes an accumulation of unwanted or misfolded proteins within the cell.
Induction of Apoptosis:
The buildup of these proteins leads to cellular stress and activation of the unfolded protein response (UPR). In cancer cells, which often have high levels of protein synthesis and turnover, this stress quickly tips the balance toward apoptosis (programmed cell death).
Disruption of Cell Signaling Pathways:
Proteasome inhibition affects several signaling pathways, including the nuclear factor-kappa B (NF-κB) pathway. NF-κB is a key regulator of cell survival, proliferation, and inflammation. Its inhibition contributes to decreased survival signals for cancer cells, enhancing the cytotoxic effects of the treatment.