Researcher studies ways cells respond to anti-cancer drugs
Jennifer Pietenpol, Ph.D. Photo by Donna Marie Jones.
A Vanderbilt University Medical Center researcher is shedding new light on the way some anti-cancer drugs work.
Jennifer Pietenpol, Ph.D., assistant professor of Biochemistry, is examining the role of the p53 gene in the cell cycle ‹ research that may one day lead to new treatment options for cancers that invade epithelial cells, including lung, prostate, colon, and cervical cancers.
"We are interested in how cells respond to the stress of DNA-damaging agents, how they set up some of the checkpoints that halt mitosis, and what some of the initial biochemical events affect," said Pietenpol.
Pietenpol recently was awarded a Burroughs Wellcome New Investigator in Toxicology Award in recognition of the promise her research holds for future developments in cancer chemotherapy.
To develop improved anti-cancer therapies, scientists must first unravel the mysteries of the cell cycle ‹ the intricate interactions between proteins and other molecules that regulate the life of a cell, including its growth and death.
Scientist often describe these molecular interactions as a balancing act that the cell performs throughout its lifetime.
³Cell growth is a balance between positive and negative signals. In cancer development, tissues are normally maintained by the balance of cell viability and cell death,² said Pietenpol.
Scientists now believe that tumor growth is, in part, caused by a lack of negative signals that normally tell a cell to stop growing. The lack of negative signals is due to genetic alterations in specific genes, Pietenpol said.
³Cancers do not form unless a genetic alteration has occurred. Recent results have shown that many of these alterations occur in genes that function in cell-cycle checkpoint. We are interested in how cells respond to DNA-damaging agents, in particular what biochemical events occur in the cell to set-up the checkpoints that halt mitosis,² said Pietenpol.
The G2/M checkpoint is one of the halting points that occurs right before mitosis. If a cell has undergone DNA damage, the checkpoint is engaged and inhibition of cell cycle progression and cell division occurs.
³A response of chemotherapy-treated tumor cells is to arrest at the G2/M checkpoint. In certain circumstances, this arrest may actually provide an advantage to the tumor cell by maintaining its viability,² said Pietenpol.
One goal of Pietenpol's research is to decipher the biochemical pathways behind the G2/M checkpoint to more effectively target chemotherapeutic drugs that will kill tumor cells instead of just arresting them at the checkpoint.
Understanding the G2/M checkpoint may allow scientists to develop more drugs that induce tumor cell death.
One drug that may be inducing cell death through this process is Taxol, currently being used nationwide as an anti-cancer agent. Still, the exact biochemical mechanisms behind its actions are not known.
³Taxol puts a cell beyond the G2/M checkpoint . Once beyond this checkpoint, the tumor cell is extremely sensitive to DNA damage and dies,² said Pietenpol. ³We hope to further expand the realm of knowledge not only for this drug but for future drugs that can be developed along these lines.²