ABSTRACT
In patients with small cell lung cancer (SCLC), little progress has been made in improving outcome in patients with extensive stage disease beyond that achieved with cisplatin and etoposide, with median survival still only 8 to 10 months. Since only a minority of patients with lung cancer respond to therapy and many are elderly with significant comorbidity, there is a need to identify agents that individually or in combination with existing cytotoxic or biologic drugs can improve outcome without a significant negative impact on quality of life. Impaired apoptosis is a hallmark of malignant transformation and lung cancer is no exception. Inhibition of the ubiquitin-proteasomal pathway can lead to growth inhibition, cell cycle disruption, and apoptosis. The proteasome inhibitor bortezomib is a boronic acid dipeptide that reversibly interferes with the chymotryptic-like activity of the 20S proteasome and immunoproteasome.
