Proteasome inhibitors in lung cancer.

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

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.

PMID: 16427303 [PubMed - indexed for MEDLINE]