July 12, 2018 By: MONICA GINSBURG
Fighting
cancer requires a one-two punch: killing cancer cells and stopping their
movement before they spread to other areas in the body. New research led by
teams from Northwestern University and Oregon Health & Science University
shows that it may be possible to significantly slow down the growth of cancer
cells, potentially making them easier to target with existing treatments like
chemotherapy and radiation.
The
study, published in
June in the journal Nature Communications, also includes
researchers from Xiamen University in China, University of Chicago and the
University of Washington. Research funding was provided by the Department of
Defense and the Veteran's Administration.
“Cancer cells are lethal because they move; they're alive,” says Karl Scheidt, director of the Center for Molecular Innovation and Drug Discovery at Northwestern University, and co-leader of the study. “How do we slow down that process? That has been the Holy Grail to figure out. We're looking at a completely different way of treating the disease.” Here's what else he had to say:
“Cancer cells are lethal because they move; they're alive,” says Karl Scheidt, director of the Center for Molecular Innovation and Drug Discovery at Northwestern University, and co-leader of the study. “How do we slow down that process? That has been the Holy Grail to figure out. We're looking at a completely different way of treating the disease.” Here's what else he had to say:
Crain's:
Why is this drug so important?
Scheidt: The
majority of cancer treatment therapies today are directed toward killing
cancer. No one has developed a therapy that can stop cancer cells from moving
around the body. Movement is key. For the vast majority of cancer—breast,
prostate, lung, colon, and others—if it's detected early when it's a small 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, it can be treated but it
will take your life. Once we can slow down cell movement, it can potentially
supercharge other treatments like chemotherapy, radiation and whatever else is
part of the current standard of care, because it will be easier to hit the
cancerous targets.
What
have you found so far?
In
animal tests, the drug is highly effective so far against four cancer types:
breast, colon, lung and prostate. It's shown to stop the spread of cancerous
cells in animal models by up to 90 percent. The data is really promising and
we're excited about the possibilities. Ultimately we want to leverage what
we've learned about the fundamentals of cell motility or movement to control
other processes in the body beyond cancer.
How did
you start working on this drug?
Ten
years ago, I met Ray Bergan, who was at Northwestern at the time and an
oncologist at the Lurie Cancer Center. He was studying motility in cancer cells
and I was interested in his work. We thought that together we could develop a
drug that would inhibit the movement of cancer cells. (Bergan is now the
Division Chief of Hematology and Medical Oncology and professor of medicine at
Oregon Health & Science University and led the study with Scheidt.) A
clinician and a basic scientist working together was very unusual at the time
but Northwestern and Lurie are really spectacular at encouraging that type of
collaboration.
We
started by taking a clue from nature. Men in Asia who were eating a diet rich
in soy were found to have a lower rate of prostate cancer. Ray was working with
genistein, a key ingredient in soy and the compound that has been used for
years in motility studies. But there were too many side effects and other
issues, so it could never be used in clinical studies. What we developed was a
new molecular entity, KBU2046, which improves on the anti-motility
characteristics of genistein. Through chemistry, we were able to enhance the
good and mitigate the bad side effects seen with the original natural product
genistein.
How
does it work?
The key
to this drug is engaging the heat shock proteins, the 'cleaners' of a cell. The
drug binds to these cleaner proteins, which changes their shape. Since these
heat shock proteins are no longer the proper shape, they don't work normally.
The ultimate impact is that it decreases the ability for tumor cells to move.
Less movement equals less metastasis which equals potentially more effective
treatments for cancer by containing the disease to a local area as opposed to
it spreading throughout the body.
What's
next in the process?
Four
years ago, Ray and I started Third Coast Therapeutics, based here in Evanston,
to help bring the drug to market and we have an exclusive option at
Northwestern to develop the technology. We are in the process of raising a
Series A round of funding to get to clinical trial. Funding is always a
challenge. Our best estimate is that will take two years and $5 to $10 million
in funding. As our first initiative, we are going to go after triple negative
breast cancer, a highly aggressive disease with very few treatment options and
a high recurrence rate. Once we see the impact, the door is then open to treat
lung, prostate, colon and other cancers. We hope in the next five years this
drug will be available to help enhance cancer treatment in patients. We think
it can change how oncologists and patients treat this disease and we hope it
will tip the scale in favor of the patient so you have more time on the clock
and a better quality of life.
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