"Because liver cancer has a very low five-year survival rate, it is most likely that even sorafenib alone may not be effective to cure the cancer," said Lin, also an investigator in Ohio State's Comprehensive Cancer Center and the Center for Childhood Cancer at Nationwide Children's Hospital. "We hope that using both drugs together could be more effective. Both celecoxib and sorafenib are already approved by the FDA, so we think this combined treatment should be able to be used in the clinic pretty quickly."
The fifth most common cancer in humans, liver cancer remains one of the most difficult to successfully treat. Patients' overall five-year survival rate is about 10 percent, according to the American Cancer Society.
These experiments were conducted in cell cultures. Further testing would be needed to determine celecoxib's effectiveness in human cancers, Lin noted.
And the powerful computational work led by Li, also an investigator in Ohio State's Comprehensive Cancer Center, is likely to lead to the development of new molecules with even more precise structural relationships with the proteins they are designed to block.
Li's method is called Multiple Ligand Simultaneous Docking. In this work, he used computer simulations to identify "hot spots" on the STAT3 protein tiny pockets to which molecules could most successfully attach to inhibit the protein's activity. He then searched through drug banks containing more than 7,500 existing and experimental medications to find the most suitable molecular fragments that could be pieced together to produce a new molecule shaped in such a way that it would fit into those pocket
|Contact: Jiayuh Lin|
Ohio State University