Bortezomib is the first-in-class proteasome inhibitor which has been used worldwide for the treatment of multiple myeloma
and mantle cell lymphoma. Bortezomib is under evaluation as a single agent or in combination with other drugs for solid cancers and
stem cell transplantation in clinical settings. However, adverse effects and drug resistance have been observed in patients, which is now
emerging as a great challenge for the extended application of bortezomib. In this review, we will comprehensively discuss the development
of bortezomib, the mechanism underlying its therapeutics, adverse effects and resistance. Second generation of bortezomib and its
future directions will also be discussed.