RICHMOND — A new study from the Virginia Commonwealth University Massey Cancer Center could rewrite the strategy for treating end-stage colon cancer.
In a report published Thursday in the Journal of Experimental & Clinical Cancer Research, VCU researchers announced a new protein-based therapy that stops tumor growth, succeeding where old medicines failed.
Dr. Yuesheng Zhang, a Massey research professor who authored the study, which tested colon cancer cells in mice, said the discovery could point colon cancer treatment in a new direction and inspire new drugs to be invented.
“If it works out in the clinic in patient trials, this could be very, very promising,” Zhang said.
Colon cancer is the third leading cause of cancer death in the United States, following lung and prostate cancer in men and lung and breast cancer in women. The American Cancer Society recommends people begin regular colon cancer screenings at age 45.
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In the early stages of colon cancer, the tumor remains localized in the colon, and doctors can simply remove it. But in the third and fourth stages , after the cancer has spread to other organs, surgery is not an option.
For years, doctors used monoclonal antibodies such as cetuximab and panitumumab to treat late-stage cancers in the colon, head and neck.
But after several months or a year, the colon cancer often becomes resistant to these drugs, allowing the cancer to keep spreading.
Experts couldn’t pinpoint why. They suspected that mutations in the cancer’s genes were to blame. But this research shows that the mutations are unrelated to the medicine’s failure.
Instead, the drug is failing to perform its main function of blocking certain proteins called epidermal growth factor receptors. In other words, it’s not the cancer — it’s the drug.
“The drug is not good enough in targeting these receptors,” said Zhang, who collaborated with Lu Yang, a VCU professor of pharmacology and toxicology, and five researchers from Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.
Armed with the knowledge of why certain drugs fail, Zhang and his collaborators discovered a new protein-based therapy — strands of DNA inserted into bacteria, called PEPD-G278D. Zhang and his team have studied the therapy for years and found out that it destroys the EGFR protein that is responsible for tumor growth.
In just a matter of hours in a controlled setting, the medicine broke down the molecule.
But the medicine has been tested only in mice. Sometimes, medicines that work on mice don’t work on humans, Zhang said.
That’s why the principle behind the therapy, and not the medicine itself, is more important, he said. Perhaps other chemotherapies can stop EGFR growth if mixed with his new therapy. The research could serve as a starting point for rethinking late-stage colon cancer treatment.
The new therapy won’t work on every colon cancer patient. About 60% of late-stage colon cancer patients have a high number of EGFR molecules on their cancer cells.
But the new therapy could also work in some breast and lung cancers, which display similar characteristics to colon cancer. Because the medicine hasn’t been tested on these cancers, it’s just a theory.
While Zhang and his team haven’t tried their protein-based therapy on humans yet, they hope to do so in a first phase of trials within two years.
