“Their version of integrative medicine means that you get what works,” says Dr. O.M. Zack Howard, Zhao’s lab supervisor and mentor. “They have clinics for acupuncture, cupping, moxibustion—you get TCM along with chemotherapy.”
Zhao’s goal: To improve the integration of traditional Chinese medicine with modern chemo- and immunotherapy.
Zhao has spent the past 2 years as an adjunct investigator in NCI’s Laboratory of Molecular Immunoregulation, part of the newly formed Cancer and Inflammation Program.
Howard met Zhao’s supervisor, Dr. Hongsheng Lin, at an international meeting hosted by NCI’s Office of Cancer Complementary and Alternative Medicine. Lin’s dedication to improving all patient outcomes by combining and standardizing Eastern and Western medicine led to their initial collaboration in 2007.
Zhao is the third scientist to visit the lab in the ongoing partnership between NCI and Guang’anmen Hospital, a clinical research center and part of the China Academy of Chinese Medical Sciences. He is the first to focus on cancer-induced hyperalgesia (increased sensitivity to pain).
His focus: Relief of cancer-induced hyperalgesia using FKI (Fufang Kushen injection), an extract of two herbal roots, Sophora flavescens and Rhizoma smilacis glabrae. FKI is widely used in Chinese hospitals to control cancer progression and cancer-related symptoms, especially pain.
His models: Both in vitro and in vivo, Zhao uses a mouse model of sarcoma, a type of cancer, injected near a major nerve.
Dr. Zhizheng Zhao (r) of China with his NCI mentor Dr. O.M. Zack Howard
Photo: Belle Waring
The data has shown that FKI can both reduce pain and inhibit tumor growth in the mouse. So Zhao combined FKI with doxirubicin, the standard of care for sarcoma, to look for the best combination therapy. With Howard’s help, Zhao’s experiments showed that doxirubicin and FKI use signaling pathways that counteract, rather than support, each other. As a result, Zhao has not yet succeeded in finding the best drug combination therapy.
Still, Howard said, “He gave us an idea of how FKI works. And now that we know how it works, we can identify tumors that would be likely to respond to it.”
Zhao’s model confirms existing mechanisms for cancer-associated pain. “He also showed us,” says Howard, “that this tumor itself, while it can destroy the region around the nerve, doesn’t actually invade the nerve until very late…This means that there are aspects of the inflammation that do destroy the nerves. And [since we are] a cancer and inflammation program, that’s important for us.”
As one of the body’s normal defenses against infection or injury, inflammation attracts immune cells. That’s acute inflammation—the helpful kind. But chronic inflammation is associated with tumor cell survival. Both types of inflammation contribute to pain.
“He came to us with a great understanding of systems analysis,” she continues. “He’s leaving us with some understanding of how systems and reduction of sciences can complement each other to come up with a better way to target cancer.”
A systems approach such as TCM looks at the whole. Western science, on the other hand, relies on reductionism, which dissects an area of study into its components and eliminates as many variables as possible.
“Here,” Zhao explains, “some of the labs are working on one molecule for a very long time, believing that there is one major signal pathway. But I think there are multiple things happening in those models.”
A signal pathway is a route for cells to perceive and communicate with each other using specialized signaling proteins.
These signaling proteins activate cascades, which act like exquisitely complex waterfalls to create still other proteins. Some, for example, carry messages vital to immune response.
This is important, because glitches in cell signaling are responsible for diseases such as cancer.
At Guang’anmen Hospital, Zhao says, “We were trying to use a [herbal] mixture, because we were not recognizing them as single components. We try to use TCM to treat patients and even in benchwork we were trying to find a couple of mechanisms.”
Before his funding ends this month, Zhao will visit the University of Texas MD Anderson Cancer Center to see how its integrative medicine program works.
“We have to get his paper out before then,” Howard says, “and we hope that when he gets back to China he has a job and funding to do his research.”
The life of a young scientist is full of creative struggle, uncertainty and sacrifice: Zhao has not seen his family in China for 2 years. Yet even as he gives due respect to his former chief of oncology in Beijing, Dr. Hongsheng Lin, he has become part of NIH’s extended family.
“My supervisors here, they were very caring,” he says. “We get better training here, not only in scientific techniques, but [also] in your future plans. It’s a good model for how we should do things in China to train our next generation, to make people think.”