Powel H. Brown, MD, PhD

2008-2009 BCRF Project:
Dr. Brown and his team of researchers have been testing novel targeted therapies for the prevention of estrogen receptor-negative (ER-negative) breast cancer. His group has shown that several different molecularly targeted drugs can prevent ER-negative breast cancer in laboratory models, and he has tested several of these in human clinical trials. However, while these drugs do delay the development of ER-negative breast cancer in the models, they do not absolutely prevent breast cancer. This may be because they do not eliminate the precursor to cancer, the cancer stem cells.

In this study Dr. Brown will investigate the effect of several different classes of cancer prevention agents on the breast cancer stem cells. In his first aim he will test these agents as single agents to determine which of these cancer prevention drugs most effectively eliminates the cancer stem cells in models that develop breast cancer. In the second aim he will test whether combinations of these agents more effectively eliminate breast cancer stem cells. Through these studies he will identify which combinations of drugs are most effective at eliminating cancer stem cells and which will totally prevent the development of ER-negative breast cancer.

Mid-year Progress Report:
Dr. Powel Brown and his team of researchers have been testing novel targeted therapies for the prevention of estrogen receptor-negative (ER-negative) breast cancer. His group is investigating whether cancer preventive agents eliminate or suppress the function of cancer stem cells in laboratory models. In this study Dr. Brown is investigating the effect of several different classes of cancer prevention agents on the breast cancer stem cells. He is treating models with cancer preventive to determine which of these cancer prevention drugs most effectively eliminates the cancer stem cells in models that develop breast cancer.

Over the last 6 months, Dr. Brown developed assays to measure the expression of cancer stem cell markers in model and human breast cells, and has conducted experiments to investigate whether cancer preventive agents suppress the number and function of cancer stem cells in models. In these ongoing experiments models that develop breast cancer are being treated with several cancer preventive agents (synthetic Vitamin A derivatives, signal transduction inhibitors, and Vitamin D analogs) and their mammary glands are harvested to determine whether these agents reduce the number and function of cancer stem cells. Over the next 6 months, he will combine these agents to discover whether combinations of drugs are more effective than single agents alone. Through these studies he will identify which combinations of drugs are most effective at eliminating cancer stem cells and which will totally prevent the development of ER-negative breast cancer.

Bio:
Dr. Powel Brown is a medical oncologist and physician-scientist specializing in breast cancer treatment and prevention at the Breast Center at Baylor College of Medicine. He is a member of the Departments of Medicine and Molecular and Cellular Biology and is also the leader of the Cancer Prevention Program of the Cancer Center at Baylor College of Medicine. Dr. Brown's laboratory and clinical efforts are focused on developing more effective ways to prevent breast cancer. In the laboratory, Dr. Brown is discovering how growth factors and hormones induce changes in gene expression that lead to the development of breast cancer. In the clinic he is developing and testing novel strategies for the prevention of breast cancer.

In the laboratory, Brown has successfully identified several signaling pathways that are critical for breast cancer development, and has used novel designer drugs (signal transduction inhibitors) to prevent breast cancer in animals. In the clinic, Dr. Brown has translated these findings to human clinical trials. In his current trials, promising cancer preventive agents are being tested for their ability to suppress the growth of normal and preinvasive breast cancer cells. Those designer drugs that successfully suppress breast cell growth will then be tested in large-scale clinical trials for their ability to prevent breast cancer. Through this work Dr. Brown plans to develop new ways to totally prevent breast cancer.