Molecular targeted agents in non-small-cell lung cancer.

Although advances in chemotherapy have provided some improvement in overall survival for patients with advanced non-small-cell lung cancer (NSCLC), outcomes remain poor. Several targeted therapies for lung cancer are in development, and it is hoped that these new approaches will continue to improve survival for patients with advanced NSCLC. These new therapies are targeted specifically to the molecular pathways and processes that characterize tumor growth and progression, including uncontrolled cell growth, invasion, metastasis, angiogenesis, and resistance to apoptosis. Some molecules, such as protein kinase C and the epidermal growth factor receptor-tyrosine kinase, play central roles in cellular activity and are involved in many of the different signaling pathways underlying malignant transformation. Other molecules are dedicated to a specific process, such as the role of vascular endothelial growth factor in angiogenesis. New approaches use a variety of technologies to target these molecules, including small-molecule inhibitors, antibodies, and antisense oligonucleotides, among others. Many of these therapies are currently being tested alone or in combination with each other and with standard treatments for a variety of tumors. This article summarizes data on treatment of NSCLC with some of the agents that are the furthest along in clinical development. It is possible to envision a future in which a combination of therapies treat lung cancer on multiple fronts, significantly enhancing tumor responses and improving survival beyond current expectations.