Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% of all lung cancer cases. Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.
Despite the epidemic amongst smokers, we still know very little about the disease and therapies remain dismal. We continue to have limited understanding of the pathophysiology of this disease and a lack of a diagnostic serum marker. Gene expression profiling promises to provide a more functional molecular understanding of this disease. This information will assist in both staging, understanding pathophysiology, prognostication and therapeutic decision trees.
Surgery is the main therapeutic option for curative intent in lung cancer. However, less than 50% of patients with lung cancer present with resectable stage I–IIIA disease. In advanced disease, systemic chemotherapy prolongs survival. Combination of a platinum agent (carboplatin, cisplatin) with a cytotoxic agent (ie. paclitaxel, docetaxel, gemcitabine) is currently the most accepted therapy. A full understanding of the molecular mechanisms in NSCLC could lead to a more effective therapy for lung cancer. New agents could be developed to target specific proteins altered in lung cancer. Furthermore, it is clear from clinical that certain subsets of patients respond to different agents. Genomics can provide valuable insight into both these goals.
|Related genes of knockout cell lines|