The biology of non-small-cell lung cancer: identifying new targets for rational therapy.

Lung cancer, and in particular non-small-cell lung cancer (NSCLC), remains the leading cause of cancer death throughout the world. Almost three decades ago, the major concern was to identify whether cisplatin or cisplatin-based chemotherapy enhanced survival in metastatic NSCLC, and whether any survival benefit compensated for cisplatin-related toxicity. Over the last 10 years, significant advances have been achieved in molecular biology, including the identification of critical genes related to the pathogenesis of NSCLC, which have formed the basis for new targeted therapeutic approaches. These new approaches include novel agents against established chemotherapeutic targets such as thymidylate synthetase as well as agents that inhibit novel targets such as growth factor receptors and proteins important in angiogenesis. With the advent of genomic technologies that can identify patterns of gene expression, the hope is that therapy will be tailored to the genetic pattern of the patients's tumor, and individualized treatments that minimize toxicity and maximize efficacy can be developed.