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Grant Abstract

Grant Number: 5R21AT005145-02
PI Name: Funk
Project Title: Identification of Natural Product Inhibitors of Breast Cancer Bone Metastasis

Abstract: DESCRIPTION (provided by applicant): India has one of the lowest rates of breast cancer - and one of the highest levels of turmeric consumption - in the world. While clearly not proving cause and effect, this inverse relationship between breast cancer and turmeric consumption is of interest given existing scientific evidence that one particular chemical found in turmeric, curcumin, can prevent cancer cell growth. Completely unexplored, however, is the question of whether the natural mixture of interacting compounds present in the turmeric consumed by women in India can work together in a complex way to prevent the progression of breast cancer. Our research team is in a unique position to examine this question, having recently finished a major NIH-funded, seven-year study to isolate and carefully identify the different chemicals present in complex turmeric extracts and fractions, and then to test the ability of these complex mixtures to prevent bone erosion in arthritis. Unique observations made in these studies led to the formulation of our novel postulate that complex turmeric products (rather than purified curcumin) may be particularly effective in preventing the progression of bone metastases in breast cancer. We posit that this protective effect is due to the specific ability of complex turmeric extracts to inhibit tumor cell secretion of parathyroid hormone-related protein (PTHrP), a hormone central to bone metastasis development in breast cancer. In vitro experiments conducted within the last year in our laboratory have now proven this hypothesis and support the design of this application which will use a reductionist approach to test turmeric extracts and fractions in vivo to examine their efficacy and safety in preventing the progression of bone metastases in estrogen receptor positive (ER+) and negative (ER-) breast cancers using an animal model. PUBLIC HEALTH RELEVANCE: Scientific research evaluating the efficacy and safety of herbal products in women diagnosed with breast cancer has not kept pace with prevailing patterns of botanical use in this population. In addition, breast cancer treatments specifically targeting key signaling pathways in tumor cells (eg. PTHrP) within the bone microenvironment to limit the progression of bone metastases do not exist. Should specific extracts of turmeric be found in these pre-clinical studies and subsequent clinical trials to be safe and effective in preventing the development and spread of breast cancer bone metastases by blockade of tumor cell PTHrP expression, their use as dietary supplements could prove to be useful additions to adjuvant treatment options in women diagnosed with early breast cancer. Additionally, standardized turmeric products could also be developed for the treatment of established breast cancer bone metastases. Given the high levels of CAM use currently in breast cancer survivors, the appropriate use of a medicinal botanical in this setting could have a significant impact on breast cancer treatment.

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