Targeted therapy of non-small-cell lung cancer

In the USA, lung cancer will claim the lives of an estimated 163,000 people in 2005. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all cases of lung cancer [1]. Nearly 40% of patients diagnosed with NSCLC present with metastatic disease at the time of initial diagnosis, a stage at which long-term survival is rarely achieved with conventional systemic chemotherapy [2]. Systemic chemotherapy produces a modest survival benefit compared to best supportive care in this setting [3]. During the 1990s, several new chemothera-peutic agents were identified to have single-agent activity in lung cancer, including paclitaxel, docetaxel, vinor-elbine, gemcitabine, and irinotecan. When utilized in combination with a platinum analogue, randomized trials have not demonstrated a survival advantage with any particular regimen. Nonplatinum doublets have not been found to offer an advantage over a platinum doublet. Thus, four to six cycles of platinum-based combination chemotherapy remains the standard treatment option for the majority of patients. Unfortunately, the 1-year survival has reached a plateau of approximately 40% following administration of conventional cytotoxic agents in advanced NSCLC [4]. Both the toxicities and drug resistance that ensue following administration limit the curative potential of systemic chemotherapy. Thus, in an effort to improve survival, several molecular targets of potential importance have been identified in NSCLC and targeted for therapeutic intervention.