Graphic of DNA

Gibbs’ research suggests breakthrough in treating colorectal cancer

Researchers at Gibbs Cancer Center & Research Institute recently discovered a gene that could be a new key weapon in fighting colorectal cancer.

“There are only five-to-six major drugs available today for treatment of colon cancer, and that’s not enough,” said Timothy J. Yeatman, MD, director and president of Gibbs Cancer Center & Research Institute. “We need more drugs and more effective ones. So, we think the research we have conducted provides hope and promise of a future cure.”

Dr. Yeatman and six other Gibbs investigators recently published a paper about their findings in the June 2018 issue of Scientific Reports, which is an open access journal from the publishers of Nature. The journal publishes original research in all areas of science.

Their study involved translational new research, which means that researchers conduct bench-to-bedside studies. They start at the level of examining human genes and will continue the work until clinical trials are available for enrollment by colorectal cancer patients.

Investigators studied more than 20,000 genes in colorectal cancer tumors to find the one – PTPRS – that could be an ideal target for new cancer treatment.

“As it turns out, we found one of 20,000 proteins that appears to be associated with controlling one of the most important growth pathways of cancer,” Dr. Yeatman said. “This is the first study in colon cancer to identify this gene as being important.”

PTPRS stands for protein tyrosine phosphatase. The gene is involved in controlling the way genes talk to each other.

The gene PTPRS changes cancer cells, making it more likely they will multiply, said Jack Pledger, PhD, deputy director and associate center director for translational research at Gibbs. Pledger was one of the investigators on the PTPRS study.

“Mutations of this gene are probably very, very important to the progression of colon cancer,” Pledger said.

Think of the gene as a stereo amplifier. When the gene is turned on, it’s louder. The key is to find a way to turn down or shut off the amplifier. That’s the goal for a new type of treatment, a phosphatase inhibitor.

This new class of drugs is already being studied in clinical trials to treat other conditions, like diabetes. The PTPRS study suggests it could inhibit – or turn down – the growth of colorectal cancer. It would work as back-up support to current colon cancer therapies.

“A lot of the pathways involved in diabetes are insulin-related pathways,” Dr. Yeatman said.

Cancer relies on sugar to grow and multiply, so insulin-related pathways also are associated with the growth of cancer. This is how a drug used to help patients with their insulin production in diabetes can also help patients stop the growth of colorectal cancer.

The new drugs could make other drugs more successful in fighting colorectal cancer.

“Our data is showing that if we can block PTPRS activity, it makes colon cancer more sensitive to other drugs,” Dr. Yeatman said.

It will be several years before colorectal cancer patients can enter a clinical trial with this new treatment. It’ll then be a few years after trials begin before cancer doctors will know for certain that this new treatment is effective.

It takes time and funding to move a drug from target to therapy. Gibbs Cancer Center & Research Institute is able to do the necessary work faster than most institutions because of Gibb’s focus on translational research. They use actual human cancer tumor cells, instead of starting with animal studies.

Another reason this potential new anti-cancer drug might move to market faster is because its safety already is being studied in diabetes’ clinical trials.

“We have three more years of work to do on this gene to get it ready for a clinical trial,” Yeatman said. “We will be involved in those clinical trials, designing the trials, getting funding, and executing on them.”

The important goal is to develop a new treatment that can help colorectal cancer patients fight the disease for a long enough time that their own immune systems can take over and cure them of cancer, he said.

“Single-targeted drugs routinely fail, and you need a second hit to come in and save the day,” Dr. Yeatman said. “This is a good target for a second drug.”

You can read the full study here.