The role of proteasome inhibitors in solid tumors.

The proteasome is a multicatalytic protein complex whose principal task is the degradation of a large array of proteins within the cell. Its substrates include proteins involved in cell cycle regulation, tumor suppression, apoptosis, transcription, and angiogenesis, among others. This makes the inhibition of the proteasome a promising novel therapeutic approach to cancer treatment. Bortezomib (Velcade) is the first proteasome inhibitor to have shown anti-cancer activity and reached clinical trials. Preclinical and early clinical trials in both solid tumors and hematological malignancies demonstrate that bortezomib is a relatively well-tolerated and active agent, either alone or in combination with traditional chemotherapeutic drugs. Clinical trials that may help delineate the role of bortezomib in the treatment solid tumors either as single agent or in combination are ongoing.