Related Experiment Videos
Molecular abnormalities in lung cancer
1Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ravi_salgia@dfci.harvard.edu
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.
Insights
Recent studies reveal key molecular abnormalities in lung cancer, including oncogene activation and tumor suppressor gene loss. Understanding these genetic changes offers potential for earlier lung cancer diagnosis and novel therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer pathogenesis involves complex molecular alterations.
- Key oncogenes and tumor suppressor genes are frequently affected.
Purpose of the Study:
- To review recently identified molecular abnormalities in lung cancer.
- To discuss their diagnostic and therapeutic implications.
Main Methods:
- Literature review using Medline database (1966-1997).
- Inclusion of cited studies and reviews.
Main Results:
- Common alterations include oncogene activation (RAS, MYC, c-erbB-2, BCL-2) and tumor suppressor gene loss (RB, p53, p16INK4A).
- Specific mutations and expression changes are frequent in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).
- For example, K-RAS mutations occur in up to 30% of adenocarcinomas, and RB abnormalities exceed 90% in SCLC.
Conclusions:
- Genetic abnormalities are central to lung cancer development.
- Further understanding of these molecular changes can drive earlier diagnosis and innovative treatment strategies.