Lung cancer occurs when cells of the lung accumulate genetic mutations, causing them to divide uncontrollably to form a tumor. According to the National Cancer Institute, approximately 220,000 new cases of lung cancer were diagnosed and 160,000 lung cancer deaths were documented in the U.S. in 2009. Environmental factors account for many cases of cancer. Prolonged exposure to cigarette smoke can cause lung cancer by inducing genetic mutations. Inherited genetic factors also play a role in the development of lung cancer. Several genetic mutations and patterns involved in the development of cancer have been identified.
EGFR Mutations
EGFR is a gene which generates the EGFR protein. EGFR is expressed on the surface of cells, and responds to growth signals from the body to tell the cell to divide. Mutations to EGFR can increase its activity, so the cell is always told to divide, eventually leading to cancer.
Mutations to specific regions of the EGFR gene have been implicated in lung cancer. In a 2006 study published in the journal Cancer Cell, Dr. C. Arteaga reported that mutations to two regions of EGFR lead to its constant activation, which leads to lung cancer. Lung cancer as a result of EGFR mutation can be effectively treated by medications that inhibit EGFR activity.
KRAS
Inherited mutations to the KRAS gene can lead to lung cancer. KRAS is a gene which tells the cell to divide, and mutated forms of KRAS may be overactive so that the cell is always instructed to divide, leading to the growth of a tumor. In a 2009 study published in Proceedings of the American Thoracic Society, Dr. G. Riely reports that mutations to KRAS were identified as important in the development of lung cancer more than 20 years ago.
Riely states that mutations to KRAS can be inherited or they can be caused by exposure to cigarette smoke. He studied KRAS in 500 lung cancer patients and found mutations in 22 percent overall as well as in 15 percent of lung cancer patients who had never smoked. Mutations to KRAS can predict the response of the cancer to therapeutics which can help doctors develop a treatment strategy to control lung cancer more effectively.
Paxillin
Although EGFR and KRAS mutations are the most common genetic factors in lung cancer, a gene called paxillin also plays a role in the development of lung cancer. A hallmark of cancer is the ability of tumor cells to invade neighboring tissue and form secondary tumors in other organs, a process called metastasis. This requires regulation of adhesion proteins to allow the cells to break away from the primary tumor and adhere to other tissue to form tumors. Paxillin is an adhesion protein, and it is found to be involved in lung cancer metastasis.
In a 2008 study published in the journal Cancer Research, Dr. R. Jagadeeswaran identified several inherited mutations to paxillin which are involved in lung cancer. He found a number of mutations to the paxillin gene, corresponding to key regions within the paxillin protein. The mutations lead to an increase in the amount of paxillin protein present within the cell. The mutated paxillin also enhanced lung cancer cell proliferation, and the ability of the cancer cells to invade neighboring tissue-contributing to lung cancer development. Further research into the link between paxillin and lung cancer may allow for the development of new lung cancer drugs to treat forms of cancer with paxillin mutations.
References
- National Cancer Institute: Lung Cancer
- Cancer Cell: EGF receptor mutations in lung cancer: From humans to mice and maybe back to humans
- Proceedings of the American Thoracic Society: KRAS Mutations in Non--Small Cell Lung Cancer
- Cancer Research: Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion
