May 28, 2015 | by Elizabeth Stewart
Although science and medicine have much in common, their practitioners are immersed in work that often appears to be worlds apart. Developing cures together — that is, translating science into meaningful, effective medical treatment — requires boundless creativity and perseverance.
This journey often starts when City of Hope’s scientists and clinicians share their recent discoveries and challenges in the lab and clinic. This open forum enables them to make new connections and consider possibilities for improving treatment for patients.
One such connection was made when Karen Aboody, M.D., professor of neurosciences and a renowned translational scientist, shared advances using neural stem cells to treat cancer with Jonathan Yamzon, M.D., a urologic oncologist who spends his days treating men in the clinic. Yamzon was intrigued by the potential of this science to target prostate cancer.
As a result, a team of researchers has embraced this promising new approach as a way to cure men. Yamzon and Aboody, along with Jacob Berlin, Ph.D., assistant professor of molecular medicine, and Jeremy Jones, Ph.D., assistant professor of molecular pharmacology, are now collaborating to bring neural stem cell therapy to men fighting prostate cancer — patients in urgent need of novel therapies for their disease.
Hormone therapy is the standard treatment for prostate cancer. The approach essentially starves cancer of testosterone, which the tumors need to grow and spread. But in many men, the cells mutate to produce testosterone on their own and keep growing, in effect becoming resistant to therapy. At this point, higher doses of chemotherapy may be effective, but would be too toxic to tolerate. This is where targeted neural stem cell therapy could step in. “We’re looking to treat patients who really don’t have any other options,” Yamzon said.
Advent of a novel approach to treatment
Neural stem cell therapy has been the focus of Aboody’s research for nearly 20 years. In 2000, she published a groundbreaking study showing that neural stem cells have an inherent ability to travel to cancer cells in the brain. “The tumor cells act like magnets and pull the neural stem cells to them,” she said.
In fact, Aboody believes that neural stem cell therapy is especially promising for advanced cancers that have spread or developed resistance to treatment, because these cancers are especially alluring to neural stem cells. “It’s almost like the more aggressive the cancer is, the more the stem cells are going to go to it,” she said.
Building on these findings, Aboody applied her research to glioma, a dangerous brain cancer with no effective treatments. Her goal was to overcome the limitations posed by current treatments by using neural stem cells to find and kill cancer cells that remain after surgery, chemotherapy and radiation — cells that inevitably lead to recurrence. First-in-human clinical trials for this treatment were completed at City of Hope in 2013.
Aboody then expanded her research to investigate whether neural stem cells also home in on metastatic solid tumors — specifically breast and ovarian cancers — as well as neuroblastoma, a cancer that affects children. Just as with glioma, the neural stem cells were attracted to these types of cancer cells, making neural stem cell therapy a possibility.
Translating therapy to target other cancers
Aboody, Berlin, Jones and Yamzon plan to test several novel approaches using neural stem cells to eradicate prostate cancer. One treatment involves modifying neural stem cells to produce an enzyme. Once the stem cells travel to the tumor, patients receive an inactive drug that is converted by the enzyme into an active chemotherapeutic drug. This approach directs chemotherapy to tumor cells, limits exposure to healthy cells and decreases side effects.
“It allows us to concentrate therapy specifically at the tumor sites and provide better quality of life,” Aboody said.
In a complementary approach, Berlin is developing nanoparticles loaded with chemotherapy that attach to neural stem cells and release a payload of therapy at the tumor site. Berlin is also developing nanoparticles of gold that will be carried by neural stem cells to the tumor sites. Once at the tumor site, these will be heated with near infrared light to incinerate surrounding cancer cells. The approach may be particularly valuable for cancers that have become resistant to chemotherapy and other drugs.
Jones is focused on understanding treatment resistance in prostate cancer. He is using his deep knowledge of the molecular characteristics of the disease to help the team design appropriate preclinical studies.
The team is also exploring similar interventions to treat patients with bladder cancers. Sumanta Pal, M.D., another City of Hope urologic oncologist with an impressive track record of advancing clinical protocols, is providing clinical expertise for the bladder cancer portion of research.
Preliminary data already suggests neural stem cell therapy may be successful in prostate and bladder cancers. The team’s next step is to design and conduct preclinical studies.
“The important thing is that basic scientists and translational researchers are working closely with clinicians to design our studies with the goal of streamlining treatments to the clinic,” Aboody said.
This partnership fostered by City of Hope’s culture of collaboration and innovation is bridging seemingly separate worlds to pioneer new therapies for patients.
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