Bortezomib: proteasome inhibition as an effective anticancer therapy.

Inhibition of the proteasome results in disruption of protein homeostasis within the cell that can lead to apoptosis, a phenomenon preferentially observed in malignant cells. Bortezomib (VELCADE) is a first-in-class proteasome inhibitor developed specifically for use as an antineoplastic agent. Its first indication, for the treatment of relapsed myeloma in patients who have received at least two prior treatments and progressed on their previous treatment, was based in part on the magnitude of activity demonstrated in Phase II trials. An interim analysis of a Phase III trial demonstrated a significant efficacy advantage of bortezomib over high-dose dexamethasone in patients with relapsed myeloma. Clinical development is ongoing to investigate its activity as monotherapy and in combination regimens for the treatment of non-Hodgkin's lymphoma, solid tumors, and early presentations of myeloma.