Sequencing bortezomib with chemotherapy and targeted agents.
The 26S proteasome is a multicatalytic threonine protease complex that is responsible for intracellular protein turnover in eukaryotic cells. This complex degrades and processes proteins required for regulation of various cellular functions. Bortezomib is a novel proteasome inhibitor approved for therapy of multiple myeloma. Inhibition of ubiquitin-proteasome-mediated protein degradation by bortezomib leads to accumulation of its diverse substrates, including cyclins, transcriptional factors, tumor suppressor proteins, and protooncogenes. The sequelae of such profound perturbation of cellular function include cell cycle arrest and activation of apoptotic programs. As the development of this agent continues, there is interest in evaluating its interaction with other anticancer agents. This review provides an overview of selected interactions between bortezomib and other anticancer agents preclinically and in early clinical trials.
Adjei
Alex A
AA
Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA. adjei.alex@mayo.edu
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000627:therapeutic use*; D000069286:Bortezomib; D002453:Cell Cycle / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D011719:Pyrazines / Q000008:administration & dosage* / Q000627:therapeutic use*; D025801:Ubiquitin / Q000502:physiology
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex