Purpose: To review several recently described molecular abnormalities in lung cancer and discuss their potential diagnostic and therapeutic relevance.
Design: Articles were identified through a Medline search (1966 to 1997) and studies, including reviews, were cited in the references.
Results: Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A. RAS is a 21-kd G protein and up to 30% of adenocarcinomas show mutations in K-RAS oncogene. MYC encodes a transcriptional activator and amplification may adversely affect survival in small-cell lung cancer (SCLC). The growth factor receptor c-erbB-2 is overexpressed in up to 25% of non-small-cell lung cancer (NSCLC) cases. BCL-2, a negative regulator of apoptosis, is expressed differently in some NSCLCs. Abnormalities of RB, a key regulator of cell cycle, are detected in greater than 90% of SCLCs. There is an inverse relationship in lung cancer cells between expression of RB and p16INK4A, an upstream regulator of RB. Mutations of p53, with frequencies up to 50% in NSCLC and 80% in SCLC, can lead to loss of tumor-suppressor function, cellular proliferation, and inhibition of apoptosis. The identified molecular abnormalities in lung cancer are currently used to develop diagnostics for detecting early disease, as well as to identify targets for gene therapy.
Conclusion: Genetic abnormalities involved in the pathogenesis of lung cancer are rapidly being delineated. Understanding molecular abnormalities in lung cancer could potentially lead to earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.