lung cancer
Charles Densmore, PhD
Developing and testing treatments in the laboratory for later possible clinical use is also one goal of Vernon Knight, MD, and Charles Densmore, PhD, both of the molecular physiology and biophysics department. Knowing that disruptions in the p53 pathway are the major causes of lung cancer, they have developed a method of using aerosol gene therapy to deliver functional p53 to cancerous lung cells.
This technology involves combining a positively charged molecule called polyethyleneiminine with negatively charged DNA encoding for p53. The two form a complex that can survive the harsh physiological climate of the lungs, enter the cells lining the airways, and deposit the DNA in the nucleus where it is expressed. "We found two very different mouse models of lung cancer in which we've been able to fairly consistently show inhibition," said Densmore.
One of the models is human p53 null osteosarcoma cells that are injected into the lungs of immunodeficient mice, done in collaboration with Eugenie Kleinerman at M.D. Anderson, while the other model is of mouse melanoma. "One of the things we think is going on, is that as p53 is expressed in these cells very efficiently, it leads to the up-regulation and the down-regulation of some genes that have an effect on the process of angiogenesis," said Densmore. Without angiogenesis, in which new blood vessels are formed, the tumors will starve and die.
Not content with using only one agent for aerosol therapy, these researchers are also looking at the effect of combining p53 gene therapy with radiation therapy or aerosolized treatments of chemotherapeutic drugs, including 9-nitrocamptothecin, itself in the first stages of clinical trials. "We have to build a whole structure of cancer therapy," said Knight. "We have to determine usefulness of each product as well as combinations of products
lung cancer
