Mechanisms of and potential treatment strategies for metastatic disease in non-small cell lung cancer.

Lung cancer consumes over one million lives in the world every year, with surgical resection playing a dominant role in the curative treatment of lung cancer with nonsmall cell histology. Mortality usually is the result of systemic spread of the disease, with little impact on survival when chemotherapy is applied in the adjuvant or palliative setting. Conventional cytotoxic chemotherapy has reached a plateau in efficacy. The future of treatment lies in the elucidation of the biology of lung cancer and the application of targeted therapies either alone or in combination with chemotherapy. The impact of the first generation of targeted therapies on lung cancer has been modest, with studies suggesting improvement in response rates, but no evidence of improved survival. As we expand our understanding of the mechanisms governing lung cancer progression and metastasis, we will be able to apply the growing armamentarium against this disease with a goal toward prolonging survival and increasing the chance for cure.