Thursday, August 8, 2013
Researchers at The University of Texas at Austin have developed a combination of therapies that significantly reduced the rate and size at which human tumors grow in mice.
In mice treated with the combined therapy, tumors took more than 70 days on average to grow as large as they grew in 50 days in mice treated with the next most effective therapy, the researchers reported in a paper published in the journal Molecular Carcinogenesis.“Our studies provide the proof of concept of our strategy in a mouse model of human cancer,” Karen Vasquez, a professor in the College of Pharmacy, said. “Perhaps we could extend life span by reducing the growth rate of a tumor using this therapeutic approach. It’s not a cure, but we think that it may provide an improvement over traditional chemotherapy.”
The combination studied was a chemotherapy drug, Gemcitabine, coupled with an approach that targets a cancer-causing gene. By targeting the cancer-causing gene, the therapy increases the effectiveness of the chemotherapy drug.
Chemotherapy drugs generally attack not only cancer cells, but also all fast-growing cells in the body.
The research targeted c-MYC, an oncogene that is present in much higher numbers in cancer cells compared to normal cells. While the excess number of copies of the cancer-causing gene drives the formation of the cancer, it also presents more targets for this novel therapeutic strategy in the cancer cells.
The therapy takes advantage of a cell’s attempts to correct its DNA if something goes wrong.
The researchers added a third strand to the double-stranded DNA of the c-MYC genes, forming a three-stranded or triplex DNA structure. The cell senses the unusual triplex structure as DNA damage and switches into repair mode and tries to rid itself of the perceived damage.
This opens the door for the Gemcitabine to come in and incorporate itself into the DNA, making cancer cells that have more copies of the c-MYC oncogene more susceptible to the effects of the drug.
The researchers used the combined therapy on mice that had been implanted with human colon cancer.
Vasquez and her team found that tumors did not grow as fast or grow as large in animals treated with the combination regimen compared to those treated with either agent alone. It took more than 70 days for the tumors in animals treated with the combined therapy to reach a volume of 0.85 cubic centimeters. The next most effective treatment was Gemcitabine alone, with tumors reaching the target size in about 55 days. Treatment with the gene-targeting therapy alone allowed the tumors to reach the target size in about 30 days, which was about the same result as no treatment at all.
“We would like to expand beyond these initial proof-of-concept studies to optimize the treatment conditions to maximize the efficacy of the combination chemotherapy regimen,” Vasquez said.
The approach also holds the promise that such treatments, by targeting the cancer-causing genes, could have fewer, less severe side effects than conventional chemotherapy.
Vasquez is one of several researchers in the College of Pharmacy who are investigating the causes of cancers and how to treat them. Other work in her lab focuses on understanding molecular mechanisms involved in genetic instability and cancer origination.
The research was funded by MD Anderson Cancer Center, where Vasquez was a researcher before coming to UT Austin, and the Goodwin family of Houston.