Molecular genetic studies of
lung cancer have revealed that clinically evident
lung cancers have multiple genetic and epigenetic abnormalities, including DNA sequence alterations, copy number changes, and aberrant promoter hypermethylation. Together, these abnormalities result in the activation of oncogenes and inactivation of tumor-suppressor genes. In many cases these abnormalities can be found in premalignant lesions and in histologically normal lung bronchial epithelial cells. Findings suggest that
lung cancer develops through a stepwise process from normal lung epithelial cells towards frank
malignancy, which usually occurs as a result of cigarette smoking.
Lung cancer has a high morbidity because it is difficult to detect early and is frequently resistant to available
chemotherapy and
radiotherapy. New, rationally designed early detection,
chemoprevention, and therapeutic strategies based on the growing understanding of the molecular changes important to
lung cancer are under investigation. For example, methylated
tumor DNA sequences in sputum or blood are being investigated for early detection screening, and new treatments that specifically target molecules such as
vascular endothelial growth factor and the
epidermal growth factor receptor are becoming available. Meanwhile, global gene expression signatures from individual
tumors are showing potential as prognostic and therapeutic indicators, such that molecular typing of individual
tumors for
therapy selection is not far away. Finally, the recent development of a model system of immortalized human bronchial epithelial cells, along with a paradigm shift in the conception of cancer stem cells, promises to improve the situation for patients with
lung cancer. These advances highlight the translation of molecular discoveries on
lung cancer pathogenesis from the laboratory to the clinic.