title: Commentary on "Proteasome Inhibitors: A Novel Class of Potent and Effective Antitumor Agents".
abstract: The relatively recent clinical success of bortezomib, particularly in multiple myeloma, has established the validity of the proteasome as a viable target for anticancer drug development. This highly cited 1999 Cancer Research article from Adams and colleagues was published during the period when this drug was transitioning from preclinical studies to phase I clinical trial status. Their results detail structure-activity analyses using a series of boronic acid proteasome inhibitors and correlate cytotoxicity with inhibition of proteasome activity. In and of itself, the recognition that interference with proteasome functions represented a novel therapeutic approach likely underlies the popularity of this article. In addition, the provision of in vitro (at that time using the NCI 60 cell line panel) and in vivo antitumor activity, toxicology, and mouse pharmacokinetic and pharmacodynamic data provided a solid basis for establishing the future credentials for bortezomib to gain initial FDA approval in 2003. Cancer Res; 76(17); 4916-7. ©2016 AACRSee related article by Adams et al., Cancer Res 1999;59:2615-22Visit the Cancer Research 75(th) Anniversary timeline.
authors: Department of Cell & Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina. tewk@musc.edu.
authors: Kenneth D
authors: KD
authors: Tew
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001897:Boronic Acids / Q000493:pharmacokinetics*; D000069286:Bortezomib; D051379:Mice; D009101:Multiple Myeloma; D011480:Protease Inhibitors; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex