Abstract ES9-2: Understanding the Role of Botanicals in the Management of Breast Cancer

Botanical agents have been used for centuries based on empiric observations of salutary effects on a variety of illnesses. A significant portion of our modern pharmacopeia is derived from botanical products and may be attributable to bioactive components that have evolved over time to protect plants from infection and pestilence or even promote health of consumers to better spread seeds or pollinate. However, whole botanicals and combinatorial formulas are still used worldwide and represent a small but growing area of research in Western medicine. One potential advantage of this approach is that synergistic combinations of compounds may have developed over time through natural selection. Drawbacks include lower potency and higher potential for drug interactions with numerous compounds. Many Chinese herbs that have been used historically to treat cancer on an empiric basis do in fact possess anti-proliferative and pro-apoptotic properties. A variety of effects on cell signaling, oxidative stress, and metabolism have been reported. As with any foreign compound, the induction or suppression of metabolism enzymes and membrane transporters can lead to significant drug interactions. Contemporary research strategies for testing botanicals must therefore incorporate hypotheses based on early clinical or laboratory observations as would be the case for a chemical compound. However, complex effects that involve host interactions are not testable via in vitro models, posing a problem with efficient prioritization of clinical trials. Drug interaction models need to be applied early on prior to clinical testing. Investigational new drug (IND) processes for botanicals are still in flux, but becoming more transparent and increasingly requiring proof of product consistency. The botanical BZL101 is an extract of Scutellaria Barbatae (Ban Zhi Lian) that has shown in vitro and in vivo growth inhibition of breast cancer cells, and causes diverse effects including tumor-specific induction of reactive oxygen species, oxidative DNA damage and necrotic cell death mediated by poly (ADP-ribose) polymerase (PARP) activation, NAD consumption, inhibition of glycolysis, ATP depletion and ultimate energetic collapse. Two Phase I trials have shown that this agent can be given safely, with mild gastrointestinal side effects and Phase II trials are planned based on early evidence of clinical benefit. In the area of symptom management, amelioration of acute irinotecan gastrointestinal toxicities has been demonstrated in mice using an ancient 4-herb Chinese formulation termed PHY906, the chemical constituents of which exhibit pleiotropic effects including inhibition of nuclear factor kB, cyclooxygenase-2, and inducible nitric oxide synthase. For menopausal climacteric symptom relief, several modern botanicals have been show to be only marginally effective, and some demonstrate estrogenic activity. A 22-botanical formula called Menerba that induces estrogen receptor-beta specifically has been preliminarily shown to reduce hot flashes to a greater extent compared to placebo, and a Phase III trial is in progress in healthy women with hot flashes. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES9-2.