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Inhibiting lung cancer with DNA-binding polyamides

Institution: California Institute of Technology
Investigator(s): Amanda Hargrove, B.S.
Award Cycle: 2010 (Cycle 19) Grant #: 19FT-0105 Award: $44,500
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
According to the American Cancer Society, lung cancer is more lethal than any other type of cancer. Nearly 160,000 deaths are estimated to have resulted from lung cancer in the United States in 2009. Research suggests that one reason these cancers do not respond well to current treatments is that lung cancer cells spread more rapidly than other cancer cells. In healthy cells a careful balance is maintained between proteins that promote cell growth and reproduction and proteins that promote cell death. This balance is disrupted in cancer cells resulting in an increase in proteins that lead to cancer cell growth and reproduction. While the majority of current and proposed cancer treatments attempt to control the behavior of these proteins in cells, more effective treatments may be possible by controlling the production of these proteins. Each cell contains numerous types of proteins, each with a specific function. All protein production begins in the nucleus of the cell when a particular transcription factor protein (TF) binds to specific sections of DNA. These sections contain codes for the production of specific proteins. The TF then essentially “reads out” the codes for the proteins that correspond to each DNA section and sends the information to other areas of the cell that can make those particular proteins. It has been proposed that blocking the binding of these TF’s to the sections of DNA that contain the code for proteins that promote cancer cell growth and/or prevent cancer cell death would lead to a reduction in the ability of cancer cells to survive and spread. Researchers have recently identified the Hedgehog pathway as a chain of proteins that activate the TF that ultimately sends the codes for the production of proteins needed for the growth and reproduction of lung cancer cells. The Dervan laboratory has developed a class of molecules that when introduced to a cell can bind with a section of DNA and block a TF from reading a specific code. This project proposes the development of one of these molecules that will bind to DNA and block the Hedgehog-related TF from “reading out” the codes for the production of the proteins that are necessary for lung cancer cells to grow and spread. If the outcome of this research is successful, it may lead to an effective treatment and a more positive outcome for patients diagnosed with lung cancer.