Bortezomib, a
boronic acid, is a potent and selective
proteasome inhibitor. The
20S proteasome is an
enzyme complex present in cells, and it degrades many cell-cycle control factors, signal transduction
factors, transcription factors, and oncogene and anti-oncogene products, thus controlling cell proliferation, differentiation, and apoptosis.
Bortezomib is a novel molecular targeting agent which was designed to exhibit an antitumor effect by selectively inhibiting the
20S proteasome.
Multiple myeloma is one of the incurable B-cell
malignancies that continues to relapse with current treatment modalities, and the duration to progression becomes shorter in patients who repeatedly receive
chemotherapy. There are no available treatment options in which durable efficacy can be expected after relapse; therefore, an effective
therapy with a novel mechanism of action has been desired. In this review article, the results of clinical trials of
bortezomib for
multiple myeloma, including a Japanese phase I/II and pharmacokinetic/pharmacodynamic study, and those for
non-Hodgkin lymphoma, especially for
mantle cell lymphoma, are summarized. In the Japanese phase I/II study of
bortezomib for relapsed
multiple myeloma, this agent showed remarkable efficacy, with acceptable toxicities and unique pharmacokinetic/pharmacodynamic profiles, warranting further investigations, including more relevant administration schedules.