Posted March 1, 2013
Gene Bidwell, Ph.D., University of Mississippi, Jackson, Mississippi
FY07 Era of Hope Postdoctoral Award
Most chemotherapy drugs are not specific to the tumor cells they are being used to treat, meaning that the chemotherapeutic agent has lethal effects in all cells in the body. Dr. Gene "Lee" Bidwell is working on a new drug delivery system that can preferentially deliver chemotherapeutics to cancer cells, concentrating the toxic effects at the tumor site, sparing normal cells, and reducing treatment side effects. Dr. Bidwell talks about his BCRP-funded research:
How is your research addressing the problem of toxic side effects?
We are developing a drug carrier that responds to heat and can be loaded with many types of chemotherapy drugs. The drug carrier with attached drug is administered by intravenous injection followed by application of a very mild heat (about 107 degrees Fahrenheit, just hotter than a high fever) at the tumor site. As the drug carrier circulates through the heated tumor, it forms large aggregates that get "stuck" in the tumor. When the heat is later removed, the aggregates dissolve and deliver the attached drug to the tumor cells.
In addition to this carrier, we are developing a type of anti-cancer agent called a peptide. Peptides are promising because they can be used to target any molecular pathway of interest and they can be very specific for that pathway. The agent we are working with now is specific for a protein that is often over-produced by cancer cells. Inhibiting this cancer-specific protein, therefore, will have a greater effect on the cancer cells and tend to spare normal cells of the body.
What have you accomplished so far and what is the next step to bringing your research closer to helping breast cancer patients?
With our DoD BCRP funding, we were able to validate our thermal targeting approach in an estrogen receptor-positive mouse model of breast cancer. We demonstrated that heat targeting can be used to increase the levels of our drug carrier in breast tumors in these mice. Further, we showed that the thermally targeted anti-cancer peptide can greatly reduce the progression (75 percent reduction relative to untreated tumors) of these tumors.
The next step is to test this thermally targeted anti-cancer peptide in other models of breast cancer to define what patient population(s) might benefit from treatment with this agent. After validation in multiple mouse models, we would next test our agent for safety in other larger animal models before advancing to clinical testing.
What barriers do you face in your research?
Increasingly sensitive and sophisticated molecular technology makes it possible to identify numerous potential treatment targets in individual tumors and patients; however, it is difficult to develop personalized conventional small molecule chemotherapeutics to home in on these targets.
Peptides have an advantage in that it is relatively easy to generate a peptide that will modulate a desired protein just by looking at that protein's sequence. The drawbacks of peptides are that they degrade quickly in the body and they do not penetrate into tumors well. For these reasons, there are not many peptides in clinical use today. By fusing them to our carrier, we can protect peptides from degradation and we can increase their uptake in tumors. We see peptides as very powerful potential drugs and are working to overcome these issues to make peptides available as clinical therapeutics.
How did this award help advance your research and your career as a breast cancer researcher?
With the support of the DoD fellowship during my postdoctoral training, I was able to demonstrate that I could perform quality science and publish high-impact results. After finishing my DoD-funded fellowship, I received a tenure track faculty position as Assistant Professor of Neurology at the University of Mississippi Medical Center. My DoD award not only allowed me to do interesting and cutting-edge science, it also prepared me to lead my independent research lab.
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