Nowadays, you can find encapsulated forms of anything, from concentrated garlic to “Super-Power Tomato” to the more generally encompassing “Essence of Love.” A quick walk down the Natural Remedies section of Whole Foods Market should be enough to instill doubt into the firmest believers of a safe and effective traditional, herbal approach to pharmaceuticals.
A new study published by Yale researchers in August 2010 would claim otherwise. PHY906, an encapsulated form of the traditional Chinese mixture called “Huang Qin Tang,” was found to significantly reduce the gastrointestinal side effects of chemotherapy, provoking the questions: Can traditional Eastern approaches to medicine teach us anything about treating cancer today? What about merging the two?
East Meets West
Chemotherapy, pharmaceutical drug treatment designed to cure or control cancer and its symptoms, is used for over half of all cancer patients in the United States today. It is often used in combination with radiation or surgery in addition to being a combination itself of several different drugs, each either treating a different part of the cancer or working to treat the same cancer in a different way. “The name of the game in cancer therapeutics is that many times you cannot use just one drug, but you need to use combinations of drugs,” says Dr. Alan C. Sartorelli, Alfred Gilman Professor of Pharmacology at the Yale School of Medicine. In theory, the best chemotherapy would involve drugs of several different synergistic mechanisms of action, resulting in a treatment that targets the cancer harder than normal tissue with less toxicity to the patient.
The toxicity involved with chemotherapy has a poor reputation—for good reason. Even when used in combination, a drug designed to affect cell division or destroy cancerous tissue usually causes significant damage to other parts of the body. Common side effects, including gastrointestinal damage, immune system depression, hair loss, decrease not only the patients’ quality of life but also their abilities to fight the cancer.
A 1,800-year-old formula of four herbal ingredients including peonies, skullcap, Chinese dates, and Chinese licorice, PHY906 was found to decrease the inflammation of intestinal tissue caused by chemotherapy in mice, enhance anti-tumor activity in the experimental mice’s bodies, and provoke the growth of new intestinal cells, thus promoting damaged tissues’ recovery. “We can conclude that this formula exerts multiple, unique mechanisms due to the presence of multiple actions,” states Dr. Yung-Chi Cheng, principal investigator of the study. The precise chemicals involved are still under current investigation, but, in a field populated with single-mechanism treatments, the implications of these findings are weighty.
Reductionist Approach in the Pharmaceutical Industry
The business of pharmaceutical discovery and production was always, without a doubt, a business. Having served as the director of the Yale Comprehensive Cancer Center as well as being a scientific advisor to several drug discovery companies, Dr. Sartorelli understands intimately that it is often impossible to separate medical research from the market forces that guide it. Even universities cannot afford to conduct clinical trials alone. Large pharmaceuticals are the ones with the fiscal ability to run these studies.
Especially for drug discovery research, funding flows more easily if a concept is feasible, not risky. Traditional medicines have had a difficult time winning over support from the pharmaceutical companies, which have generally hesitated to explore potential due to lack of an established approach for investigation. Dr. Cheng explains three major bottlenecks that diminish a drug’s likelihood of getting to market: the inability to prepare enough quality, consistent material fit for experimentation, the lack of convincing evidence to prove its efficacy, and the lack of information about the formula’s mechanism of action.
Eastern herbal-based medicines, which are often formulated to treat the patient’s condition as a whole, lack clear targets or mechanisms of action, making securing funding for the clinical experiments difficult. “If you develop a potential drug that treats lung or colon cancer, then you give them drugs that target lung or colon cancer,” Dr. Sartorelli describes. “[The U.S. Food and Drug Administration (FDA)] just [needs] to know if this drug has the potential to treat the kind of cancer the patient has.”
This reductionist “drug A treats disease B by doing C” attitude has, in Dr. Cheng’s opinion, caused many pharmaceutical companies to fail in their past forays into TCM (Traditional Chinese Medicine)-based drug development. “Too often researchers want to use a reductionist approach and isolate a single compound from a traditional formulation,” he explains. However, because each component in a traditional medicine prescription contributes to the drug’s function, Dr. Cheng believes that such attempts to replicate a TCM’s beneficiary effects with only one or two of its active components are futile. That is why he did not intend to isolate the individual components of PHY906 for initial investigation. “We processed it the same way as tradition.”
The Age of Personalized Medicine?
Dr. Sartorelli’s vision for the future of cancer treatment involves not only finding the right drugs, but also finding the right patients. “Basically, what you’d like to do is to be able to say, ‘this cancer that this patient has a high probability of responding or not responding to the drug.’ To accomplish this we will require a test able to measure the probability a patient has of responding to this drug being used.”
He believes that by dividing patients into groups of high and low probability of response before prescribing treatments will allow chemotherapy to be tailored to the individual needs of the patient with greater efficacy and lower toxicity. This approach, popularly termed “personalized medicine,” is based on the idea that no single drug can treat all patients effectively even if they have the same kind of cancer. Current research increasingly suggests that an individual’s specific genetic makeup and even living environment affects how he or she responds to the same molecule or combination of molecules. “What you can do with personalized medicine,” Dr. Sartorelli says, “is that it doesn’t matter what the kind of cancer we are dealing with but whether it possesses the drug target.”
Dr. Cheng, like Dr. Sartorelli, believes that the genetic makeup of an individual should be taken into consideration when deciding the type of drug to be used. In fact, that is where he found his inspiration for his work in traditional Chinese medicine, which possesses a structural biology basis and is prescribed to tailor an individual’s unique needs.
In the Future
“Focus is key in a complicated area,” Dr. Cheng says. For now, he plans to focus his energies on developing a comprehensive understanding of PHY906—its effects, its mechanisms, its production—rather than racing to find the next miracle mixture. While looking at the big picture was useful for estimating this compound’s therapeutic potential, determining the precise mechanism of action is needed to make the formula simpler and more effective. Dr. Cheng believes that reductionist and holist methods can be used in tandem to yield polychemical entities in future medicine, particularly for treatment of chronic diseases such as cancer.
Likewise, Dr. Sartorelli encourages ingenuity in new therapeutic approaches, while keeping optimism grounded in reality. “The idea with ‘holistic therapy’ is to use everything in our power for the benefit of the patient. I have no trouble with that—it’s all for the benefit of the patient. In terms of getting rid of the cancer, however, I have yet to see major effects with some of the most difficult cancers we get to treat.”
Nevertheless, thanks to the work of scientists like Dr. Cheng and Dr. Sartorelli, the “popular” approach to medicine is changing. In 2004, the U.S. Food and Drug Administration (FDA) passed a measure easing regulations on herbal mixtures, perhaps signaling a new openness to approving the use of medicines at low toxicity dosages even if their individual components are unknown.
Further Readings:
- Lam et. al. The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med. 2010 Aug 18; 2(45).
- Visit https://www.nfcr.org/index.php?option=com_content&view=article&id=227&Itemid=46 to learn more about breakthrough new cancer therapeutics, including Dr. Cheng’s. On the same site at https://www.nfcr.org/index.php?option=com_content&view=article&id=214%3Aalan-c-sartorelli-phd&catid=48%3Afellows&Itemid=121, Dr. Sartorelli gives a concrete example of his work in personalized anticancer medicine.
- Visit https://www.tcmedicine.org to learn more about Dr. Cheng’s global initiative to advance Eastern-Western medicine integration.
- Sharma S, et al “A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations” Cell 2010; 14: 69-80.
About the Author
Linda Wang is a sophomore Molecular Biophysics & Biochemistry major in Jonathan Edwards College. Regardless of her precise career path, she believes keeping an open mind with regards to medical practice to be paramount and someday hopes to do research that leads to innovative drug discovery.
Acknowledgements
The author would like to thank Dr. Cheng and Dr. Sartorelli for sharing a bit of their tremendous visions with her. They truly showed her what it means to have a dream and devoting your life’s work to it.