Small molecule gene regulation in lung cancer cells
Abstracts
Initial Award Abstract |
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Smoking accounts for at least 30% of all cancer deaths and 87% of lung cancer deaths in the United States. It has been estimated that in the year 2007 there were 213,380 new cases of lung cancer, with 17,920 occurring in the state of California. The majority of patients treated for small cell lung cancer developed the disease from tobacco smoking. The development of more effective treatments for lung cancer is greatly needed.
A signature trait of small cell lung and many other types of cancer is the over-activity of the MYC gene, which encodes the MYC protein. This protein then has the ability to turn other genes on or off by joining with another protein (MAX) and together binding to specific sequences of DNA. When levels of MYC protein are elevated, a variety of genes can be turned on with the common result being uncontrolled cell growth, a trademark of cancer.
In the research proposed, we hope to prevent the MYC-MAX unit from binding to those DNA sequences that result in genes being turned on. We believe that the effect of inhibiting binding will be the inability of cancer cells to continue growth and/or cell death. The protein will literally be blocked from its desired DNA position by a small molecule which has the ability to recognize and bind to specific sequences. This molecule will be designed to target only those regions of DNA that the MYC-MAX protein complex needs to reach to turn genes on. The approach described does not affect the genetic sequence or the production of MYC, but only stems its detrimental activity. We believe that this is important because a nominal level of MYC is required for the repression (or turning off) of some genes and normal cellular functioning. We plan to generate a series of DNA-binding molecules and evaluate their abilities to prevent gene activation and as anti-cancer agents toward small cell lung cancer. Should our endeavors be successful, this research may form the basis for a new method of human cancer treatment. |
