It has become increasingly apparent in recent years that a therapeutic plateau has been reached for patients with advanced stage non-small cell lung cancer (NSCLC) treated with conventional cytotoxic agents. As a result, investigators have directed their efforts toward the development of treatments encompassing novel targeted agents. Apoptosis is one of many cellular pathways currently under investigation as a therapeutic target for the treatment of NSCLC. Anti-inflammatory agents, including cyclooxygenase inhibitors, have been shown to inhibit apoptosis and appear promising based on preclinical studies. However, several phase II studies indicate that this therapeutic strategy is unlikely to be successful. In contrast, the proteosome inhibitor bortezomib has shown promise in preliminary studies, and further efforts to elucidate the role this agent may play in the treatment of NSCLC are ongoing. Agonists of the tumor necrosis factor-related, apoptosis-inducing ligand have also entered into early clinical studies in patients with NSCLC. Further studies will be needed to fully clarify how agents targeting the apoptotic pathway can be used in the treatment of NSCLC, but the results of current clinical trials suggest that certain agents may be active.
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