Proteasome inhibitors in lung cancer.
Proteasome inhibition is a novel therapeutic approach that is being investigated in non-small cell and small cell lung cancer (NSCLC and SCLC). Proteasome inhibition affects a range of intracellular signals and disrupts the levels of numerous proteins, causing apoptosis via multiple pathways. Importantly, malignant cells are more sensitive to proteasome inhibition than normal cells. A number of proteasome inhibitors have demonstrated activity in preclinical studies, both as single agents and in combination with conventional and novel antineoplastic agents. However, only bortezomib, a dipeptide boronic acid analog, has been investigated in lung cancer clinical trials, in which it has shown activity as a single agent and in combination regimens. Numerous preclinical and clinical studies are ongoing in both NSCLC and SCLC. Proteasome inhibition could potentially play a significant role in the future management of these conditions.
Scagliotti
Giorgio
G
University of Torino, Department of Clinical and Biological Sciences, Thoracic Oncology Unit, San Luigi Hospital-Regione Gonzole 10, 10043 Orbassano, Torino, Italy. scagliotti@ihnet.it
D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000201:enzymology; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*
D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex