An Oklahoma Medical Research Foundation scientist has identified novel functions for an enzyme that may play an important role in causing cancers to become malignant and resistant to drug treatment. The discovery could have clinical relevance for the treatment of cancer.
OMRF scientist Gary J. Gorbsky, Ph.D., has detailed his research in the journal Current Biology. The paper appears on the cover of the June 23 issue of the journal, one of the leading scientific publications in the area of cell biology.
Gorbsky’s work focuses on a cell signaling pathway (called the mitotic spindle checkpoint) that regulates cell division. This checkpoint ensures that each newly created cell receives the correct number of chromosomes.
In some cells, this checkpoint system fails to regulate cell division properly, causing the cells to gain or lose chromosomes more easily. And those chromosomal anomalies, says Gorbsky, have been closely linked to cancer.
“There’s little doubt that having the improper number of chromosomes in a cell contributes to both malignancy and drug resistance,” said Gorbsky, who holds the W.H. and Betty Phelps Chair in Developmental Biology at OMRF and also heads the foundation’s Molecular, Cell and Developmental Biology Research Program. “Some researchers also believe that the gain or loss of chromosomes is a primary step in the development of cancer.”
In his paper, Gorbsky reports he has pinpointed novel functions for an enzyme that regulates the mitotic spindle checkpoint. His research also indicates that defects in the regulation of this enzyme may play a critical role in causing chromosomal abnormalities. According to Gorbsky, these discoveries could lead to new strategies for treating cancer.
“One potential strategy would be to use a therapeutic agent to target checkpoint systems in cancer cells,” said Gorbsky. “Normal tissue cells with strong checkpoint systems would survive, while cancer cells with weak checkpoints would be ‘pushed over the edge’ to die.”
The success of several current cancer treatments, says Gorbsky, likely lies in a similar ability to target cellular weaknesses in cancer cells. The OMRF scientist intends to build on his recent discovery to explore further treatment options for cancer.
“This checkpoint system is a potential target for cancer drugs,” Gorbsky said. “Our lab will continue to look at ways in which we can eliminate cells with defective checkpoint enzymes. Ultimately, we hope our work will lead to more effective methods of treating deadly cancers.”
Gorbsky holds both an M.A. and a Ph.D. in biology from Princeton University. His research focuses on mitosis, the process of how cells divide, and he has earned international recognition for his work in the area of chromosomal movement.
Chartered in 1946, OMRF (www.omrf.org) is a nonprofit biomedical research institute dedicated to understanding and curing human disease. Its scientists focus on such critical research areas as Alzheimer’s disease, cancer, lupus and cardiovascular disease. OMRF is home to Oklahoma’s only member of the National Academy of Sciences.