Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018, Oregon Health & Science University
Ryan Gordon, Ph.D., and Raymond Bergan, M.D., with members of their lab. Credit: OHSU/Kristyna Wentz-Graff.

Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature Communications, shows that it may be possible to freeze cancer cells and kill them where they stand.

Raymond Bergan, M.D., Division Chief of Hematology and Medical Oncology and professor of medicine at OHSU, says that the majority of cancer treatment therapies today are directed toward killing cancer. To date, he says, no one has developed a therapy that can stop cancer from moving around the body.

"For the vast majority of cancer—breast, prostate, lung, colon, and others—if it is detected early when it is a little lump in that organ and it has not spread, you will live. And generally, if you find it late, after it has spread throughout your body, you will die," says Bergan, also the associate director of in the OHSU Knight Cancer Institute and director of the OHSU Bergan Basic Research Laboratory. "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."

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 team took a novel approach to their research by working with chemists to jointly discover a that will inhibit the movement of cancer cells. The Nature Communications paper outlines 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 and wouldn't do anything else," Bergan says. "That basic change in logic lead us to do everything we did."

A multidisciplinary team

The team of investigators includes Bergan's team at OHSU, a chemist from Northwestern University as well as researchers from Xiamen University in China, the University of Chicago, and the University of Washington. Ryan Gordon, Ph.D., research assistant professor in the OHSU School of Medicine and co-director of the Bergan lab, says drawing upon the strengths of this cross-functional group was key to the research's success. "As we identified areas we were lacking, we looked at new cutting-edge technologies, and if there was something that didn't meet our needs, we developed new assays to address our needs," he says.

The lab of Karl Scheidt, Ph.D., 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 then evaluated by Bergan's team for their ability to inhibit . Using chemical synthesis approaches, Scheidt and team accessed new compounds that minimized motility in tumor 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 says. "It's been a truly rewarding experience working together as a team toward ultimately helping cancer patients."

Refining the drug

Bergan notes the process for 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 of stopping the cells with no side effects," he says. "All drugs have side effects, so you look for the drug that is the most specific as possible. This drug does that."

Bergan says the key to this drug was engaging the heat shock proteins—the "cleaners" of a cell. "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." He says it is a very unusual, unique mechanism that "took us years to figure out."

"Initially, nobody would fund us," Bergan says. "We were looking into a completely different way of treating cancer."

Next step: testing the drug in humans

Ultimately, Gordon says the goal of this research is to look for a new therapeutic to benefit 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," he says. He's quick to note this work has not been tested in humans, and doing so will require both time and money. The team's best estimate is that will take about two years and five million dollars 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.

In addition, Drs. Bergan and Scheidt have founded a company, Third Coast Therapeutics, aimed to bring this type of therapy to patients.

"Our eventual goal is to be able to say to a woman with breast cancer: here, take this pill and your cancer won't spread throughout your body. The same thing for patients with prostate, lung, and colon cancer," Bergan says. "This drug is highly effective against four cancer types (breast, colon, lung, prostate) in the in vitro model so far. Our goal is to move this forward as a therapy to test in humans."

Bergan says his team feels lucky to have the opportunity to conduct this challenging research at the OHSU Knight Cancer Institute, an institute dedicated to novel approaches to detecting and treating .

"What early detection is trying to do is detect an early, lethal lesion. Cancers are lethal because they move," he says. "This drug is designed to stop that movement."

Explore further: New drug prevents spread of human prostate cancer cells

Related Stories

New drug prevents spread of human prostate cancer cells

April 3, 2012
A new drug developed by Northwestern Medicine scientists prevented human prostate cancer cells from spreading to other tissues without any toxic effects to normal cells or tissues. The drug turns off the "go" switch in the ...

Two drugs are better than one in fight against leukaemia

March 8, 2018
Adelaide scientists have devised a way to enhance the effectiveness of a patient's leukaemia treatment by using a combination of drugs.

Novel therapeutic target discovered for estrogen receptor positive (ER+) breast cancer

November 17, 2017
Researchers at the Icahn School of Medicine at Mount Sinai have identified a protein that can be targeted to suppress growth of a common type of breast cancer known as "estrogen receptor positive" (ER+), including ER+ cancers ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Recommended for you

Link found between bitter-taste sensitivity and cancer risk

July 18, 2018
High bitter-taste sensitivity is associated with a significantly increased risk of cancer in older British women, according to researchers who conducted a unique study of 5,500 women whose diet, lifestyle and health has been ...

Research identifies new breast cancer therapeutic target

July 18, 2018
Research led by Suresh Alahari, Ph.D., Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has shown for the first time that a tiny piece of RNA deregulates energy metabolism, an ...

Cancer patients may experience delayed skin effects of anti-PD-1 therapy

July 18, 2018
Cancer patients receiving anti-PD-1 therapies who develop lesions, eczema, psoriasis, or other forms of auto-immune diseases affecting the skin may experience those adverse reactions on a delay—sometimes even after treatment ...

Early supper associated with lower risk of breast and prostate cancer

July 18, 2018
Having an early supper or leaving an interval of at least two hours before going to bed are both associated with a lower risk of breast and prostate cancer. Specifically, people who take their evening meal before 9 p.m. or ...

Magnetized wire could be used to detect cancer in people, scientists report

July 16, 2018
A magnetic wire used to snag scarce and hard-to-capture tumor cells could prove to be a swift and effective tactic for early cancer detection, according to a study by researchers at the Stanford University School of Medicine.

Researchers suggest new treatment for rare inherited cancers

July 16, 2018
Studying two rare inherited cancer syndromes, Yale Cancer Center (YCC) scientists have found the cancers are driven by a breakdown in how cells repair their DNA. The discovery, published today in Nature Genetics, suggests ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Parsec
5 / 5 (1) Jun 24, 2018
It is a long path between a discovery like this and people being treated with medication. A path littered with legal, technical, and financial obstacles.

I hope they succeed.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.