ABSTRACT

ABSTRACT Lung carcinoma is one of the most common malignant tumors in the world, and is the leading cause of carcinoma death in the United States. Despite recent advances in understanding the molecular biology of lung carcinoma and the introduction of multiple new chemotherapeutic agents for its treatment, its dismal 5-yr survival rate (<15%) has not changed substantially. Clinical approaches such as chemoand radiotherapies have shown only a modest improvement in survival of patients with advanced disease. However, recent discoveries regarding the molecular mechanisms responsible for lung cancer initiation and proliferation have unveiled new targets for therapy. One of the hallmark features of cancer cells is their ability to evade apoptosis (also termed programmed cell death). Aberrations in pro-and anti-apoptotic pathways are common in cancer cells and defects in regulation of apoptosis have been implicated in both lung tumorigenesis and drug resistance. Th us, targeting apoptosis through the direct or indirect manipulation of the proapoptotic machinery off ers a novel strategy for treatment. Th is chapter reviews the molecular events that contribute to drug-induced apoptosis and how lung tumors evade apoptotic death followed by an analysis of the implications for treatment.