Cancer Treatments Emerge From Modern Metabolomics, Traditional Chinese Medicine

Over 1,800 years ago healers in China mixed together a formulation called Huangqin Decoctin to relieve their patients’ aches and pains. Today, colorectal cancer patients in a Phase II Clinical Trial are receiving a therapeutic treatment made from this ancient formulation. The potential new drug is being tested for its effectiveness in reducing the harsh side effects of chemotherapy that these patients experience.

This new therapeutic agent derived from Traditional Chinese Medicine (TCM) was developed with funds from a National Institutes of Health grant to the Yale School of Medicine. Wei Jia, PhD, a subcontractor on the grant and co-director of the UNC Greensboro Center for Translational Biomedical Research at the North Carolina Research Campus (NCRC) in Kannapolis, is analyzing how patients in the clinical trials metabolize the new drug. The goal is to explain how and why the drug is reducing the side effects of the chemotherapy for most of the patients in the clinical trials and may not be working as well for others.

Jia sees the testing of this new drug as one example of how TCM can merge with Western, evidence-based medicine to present a new stratagem for the diagnosis, prevention and treatment of cancer.

Where TCM and Modern Metabolomics Meet

Recruited from Shanghai Jiao Tong University, one of the top universities in China, Jia was professor of Natural Medicines and the vice dean of the School of Pharmacy. His research has spanned nuclear medicine to the study of the bioactive compounds in medicinal plants used in TCM. He and his research team have developed treatments for bone cancer and a disease similar to diabetes called Xiao-ke. Jia’s research has also shown that plant components from traditional Chinese herbs can lower cholesterol and help with weight loss.

Since coming to the NCRC in 2008, Jia’s main research focus is cancer metabolism. Metabolism is defined as the chemical reactions in the cells of living organisms. The reactions determine essential functions such as growth, reproduction and environmental response. “We are spending a lot of time and effort in the understanding of the human physiology and human metabolism associated with cancer and with metabolic disorders,” Jia explained. “Metabolism is the downstream of the whole biological process. It starts with genes regulating proteins that regulate metabolites. Metabolites are what we call footprints.”

Footprints that take into account genetic differences and environmental factors. which is important because only 30 percent of cancers are purely genetic leaving the remaining 70 percent to be triggered by environmental factors. Those factors are as varied as a person’s mood, mental condition, physiological state, diet or exposure to heavy metals, viruses, pesticides or other toxins. Metabolites also provide a broader picture of disease than biomarkers, which are traditionally proteins in the blood that can indicate the presence of a disease. Although research into biomarkers is producing some results, according to Jia, many of the biomarkers are not specific enough to establish reliable standards for diagnosis and treatment of many cancers.

At the NCRC, Jia and his research team study metabolomic profiles in human tissue or fluids like blood and urine by taking advantage of tools like a 950 MHz Nuclear Magnetic Resonance (NMR) spectrometry and state-of-the-art mass spectrometry instrumentation located in The David H. Murdock Research Institute (DHMRI), the NCRC’s core laboratory and a non-profit contract research organization.

Collaborations and Breakthroughs

Access to top instrumentation and a talented research team of scientists, postdoctoral fellows and graduate students has enabled Jia's Center at the NCRC to be one of the first to analyze blood, urine and cancer tissue of colorectal cancer patients to identify a unique metabolic profile of colorectal cancer. Jia also collaborates with MD Anderson Cancer Center at the University of Texas in Houston and the City of Hope Cancer Center in Los Angeles, CA, two of the top cancer centers in the world. For the City of Hope, Jia’s team is analyzing over 100 blood serum and plasma samples from breast cancer patients as well as samples from colorectal and liver cancer patients.

“So far people have found that all kinds of cancers are unique in terms of their metabolism,” he said. “One cancer cell and one normal cell are so different in terms of metabolism. There are unique metabolic features that we are gradually finding and understanding. As soon as we can confirm and validate those features, we can design drugs to block them and then we can stop the cancer process.”

Jia is finding broader applications for his research approach. With co-director Zhanxiang Zhou, PhD, and others in the Center for Translational Biomedical Research, Jia is part of a paper published in the September 2012 edition of the Journal of Proteome Research entitled the Transcriptomic and Metabonomic Profiling Reveal Synergist Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice. Using metabolomics, they verified the synergistic effect of the plant compounds to “prevent fatty liver and the obese phenotype.” They are also studying the compounds in an animal model to see the effects on colorectal cancer.

Jia and Mingming Su, PhD, a scientist in the DHMRI Analytical Sciences Laboratory, have discovered a breakthrough profile to diagnose gouty arthritis using trace elements. Published in March 2012 in the journal Metallomics, the paper Human Gouty Arthritis is Associated with a Distinct Serum Trace Elemental Profile describes their research into the trace amount of metals commonly related to joint disorders. Through measuring serum samples with three regionally independent groups of study participants, Su and Jia established an elemental profile of gouty arthritis. The profile has over a 95.7 percent accuracy rate for the diagnosis of gouty arthritis using only three elemental markers, Lithium, Aluminum and Uranium. The study supports that gouty arthritis has a unique elemental expression profile that is present regardless of other nutritional or environmental variables. As a result of their research, they are planning to develop non-invasive kits that will require only urine or blood to quickly screen and diagnose gouty arthritis and other diseases.

“People have so much trouble understanding cancer, diabetes, arthritis and all kinds of neurological conditions,” he said. “Many well-trained PhDs and MDs have worked for years, and so far they don’t have much of a clue. That may mean the strategy is not right.”

With research in the United States and China, Jia is working at a junction of Eastern and Western science and medicine where the benefit of such a combined approach may provide the strategies needed to usher in an era where metabolic disease pathways are better understood and natural, plant-based compounds are a new generation of effective preventatives and treatments for diseases like cancer.

For more information, visit UNC Greensboro Center for Translational Biomedical Research.