About This ProjectThe hardest part about killing cancer cells is making sure we don't kill healthy cells at the same time. We've found a key difference between some types of skin cancer cells and normal cells: the skin cancer cells can have a much higher concentration of a particular enzyme than healthy cells. Our plan: to develop a prodrug, and use that very enzyme AGAINST skin cancer cells.
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What is the context of this research?
We have found an enzyme that is found at much higher levels in melanoma cells than in normal cells. An enzyme is like a very small machine that can bind to a specific molecule and change it: much like a key can open a specific lock and unlock a function. The enzyme we have discovered is called oxidized protein hydrolase (OPH). We have designed a small molecule, called a prodrug, that is changed by the OPH enzyme into an active drug that we think can kill melanoma cancer cells but normal cells. This is very useful since our prodrug could be useful for killing melanoma cells but have minimal bad side effects. We need to make more of the prodrug by use of organic chemistry and need to more testing with melanoma cells and normal cells (cell biology).
What is the significance of this project?
Malignant melanoma is among the most lethal cancers and accounts for 75 percent of all deaths associated with skin cancer. Once melanoma has spread from the skin to internal organs it cannot be treated effectively with surgery and current chemotherapeutic drugs are of limited value. Metastatic melanoma patients have a median overall survival of less than one year There is a clear need to develop more effective and selective treatment options for melanoma.
What are the goals of the project?
We have designed and synthesized a novel prodrug that is activated by an enzyme that is higher in some melanoma cancers than in normal tissues. This prodrug is not commercially available and must be synthesized in order for our testing to proceed with melanoma cancer cells. We have a well-established cancer research team with the ability to move our research from "the laboratory bench to the bed."
We have designed a prodrug that is activated by an enzyme in melanoma cells to produce reactive forms of oxygen that should kill melanoma cancer cells. This prodrug is not commercially available and must be synthesized in order for our testing to proceed.
Meet the Team
Team BioWhen not engaged in research, I enjoy hiking the Appalachian Trail through the Cherokee Mountains of East Tennessee. My current research is focused on developing novel cancer drugs that hold the promise of reducing human suffering. I collaborate with research oncologists and pharmaceutical chemists who share this goal. Cancer has touched most families including my own.
I have held faculty positions at the University of California at Santa Cruz, Meharry Medical College in Nashville and am presently the Director of Pediatric Research and Professor of Pediatrics at the James H. Quillen College of Medicine, East Tennessee State University. I have served as the principal investigator for numerous basic science and clinical oriented research projects.
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