It May Be Possible to Freeze Cancer Cells and Kill Them Where They Stand
The majority of cancer treatment therapies today are directed toward killing cancer. However, there’s no therapy developed yet, that can stop cancer cells from moving throughout the body.
New research, published in Nature Communications, shows that it may be possible to do so, in freezing cancer cells and killing them where they stand.
“Movement is key: the difference is black and white, night and day. If cancer cells spread throughout your body, they will take your life. We can treat it, but it will take your life,” said Dr. Raymond Bergan, Division Chief of Hematology and Medical Oncology and Professor of Medicine at Oregon Health & Science University (OHSU).
For that reason, the study of cancer cell movement, or motility, has been the focus of his group’s research for several decades.
Stopping Cancer Cell Movement
In 2011, Bergan and his team took a novel approach to their research by working with chemists to jointly discover a drug that will inhibit the movement of cancer cells.
This new paper outlined the multidisciplinary team’s work with KBU2046 — a compound that was found to inhibit cell motility in four different human cell models of solid cancer types: breast, prostate, colon, and lung cancers.
“We used chemistry to probe biology to give us a perfect drug that would only inhibit the movement of cancer cells and wouldn’t do anything else,” Bergan said. “That basic change in logic lead us to do everything we did.”
Refining the Drug
The lab of Dr. Karl Scheidt, Professor of Chemistry and Professor of Pharmacology; Director of the Center for Molecular Innovation and Drug Discovery; and Executive Director of the NewCures accelerator at Northwestern University, was responsible for the design and creation of new molecules which were evaluated by Bergan’s team for their ability to inhibit cell motility. Using chemical synthesis approaches, Scheidt and team accessed new compounds that minimised motility in tumour cells, with few side effects and very low toxicity.
“We’ve taken a clue provided by nature and through the power of chemistry created an entirely new way to potentially control the spread of cancer,” Scheidt said. “It’s been a truly rewarding experience working together as a team toward ultimately helping cancer patients.”
Bergan notes the process of narrowing down the specific drug compound was a process of refinement.
“We started off with a chemical that stopped cells from moving, then we increasingly refined that chemical until it did a perfect job stopping the cells with no side effects,” he said.
“All drugs have side effects, so you look for the drug that is the most specific as possible. This drug does that.”
The key to this drug, in particular, was to engage the heat shock proteins — the “cleaners” of the cell, Bergan said.
“The way the drug works is that it binds to these cleaner proteins to stop cell movement, but it has no other effect on those proteins.” Bergan said it is a very unusual unique mechanism that “took us years to figure out”.
Testing the Drug in Humans
“The eventual promise of this research is that we’re working toward developing a therapeutic that can help manage early-stage disease, preventing patients from getting the more incurable later-stage disease,” Dr. Ryan Gordon said, who is a Research Assistant Professor in the OHSU School of Medicine and co-director of the Bergan lab.
He is quick to note this work hs not been tested in humans, and doing so would require both time and money.
“Initially, nobody would fund us,” Bergan said. “We were looking into a completely different way of treating cancer.”
The team’s best estimate is that will take about two years and $5 million of funding. They are currently raising money to do IND (investigational new drug) enabling studies, a requirement to conduct a clinical trial of an unapproved drug or an approved product for a new indication or in a new patient population.