Molecular genetics of lung cancer.
Lung cancer results from multiple changes in the genome of susceptible pulmonary cells caused by exposure to carcinogens found in tobacco smoke, the environment, or the workplace. Recent studies suggest that histologically apparent lung cancer is due to the sequential accumulation of specific genetic and morphologic changes to the normal epithelial cells of the lung. Positive signallers, such as those mediated by the oncogene RAS, and negative signallers, such as those mediated by the tumor suppressor retinoblastoma protein (RB), contribute to unchecked cell growth and proliferation. Other key molecular derangements can also be considered hallmarks of cancer, including evasion of apoptosis and senescence, angiogenesis, tissue invasion, and metastases. Epigenetic inactivation of genes via DNA methylation provides another novel way of evading normal cellular control mechanisms. The new knowledge of the human genome coupled with global methods of detecting genetic abnormalities and profiling gene expression in tumor cells may enable us to understand the signaling pathways of lung cancer cells. These are molecular targets for new cancer therapeutics such as receptor tyrosine kinase inhibitors. This information could advance risk assessment, early detection, prognosis, and therapy for lung cancer.
Sekido
Yoshitaka
Y
Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Tsurumai 65, Showa-ku, Nagoya 466-8560, Japan. ysekido@med.nagoya-u.ac.jp
Fong
Kwun M
KM
Minna
John D
JD
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004249:DNA Damage / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology; D016153:Genes, Suppressor / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008967:Molecular Biology; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000235:genetics; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics
D016160:Retinoblastoma Protein; D018631:ras Proteins