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Powel H. Brown, MD, PhD
John Charles Cain Distinguished Chair
Department of Clinical Cancer Prevention
University of Texas MD Anderson Cancer Center
Goal: To identify new targets for the treatment and prevention of triple negative breast cancer (TNBC).
Impact: Dr. Brown has discovered a protein (SOX9) that is a “master regulator” of breast cancer metastasis. His group has shown that inhibiting SOX9 stops progression of metastatic disease in laboratory models.
What’s next: He and his team are now attempting to develop a small molecule inhibitor—a type of drug that easily enters cells and may cause cancer cells to die—of SOX9 that can be used in humans for the treatment and prevention of breast cancer metastases.
TNBC is an aggressive form of breast cancer with a high likelihood of spreading to other tissues. There are few treatment options for these patients beyond chemotherapy, since TNBC lacks receptors that respond to hormone-based therapies. Dr. Brown is conducting laboratory experiments that will inform the development of new therapeutic strategies to treat or prevent the spread of TNBC.
Full Research Summary
Research area: Developing novel therapeutic targets for the treatment of triple negative breast cancer (TNBC), an aggressive form of the disease with a high likelihood of spreading to other tissues.
Impact: TNBC is difficult to treat because the tumors lack the estrogen, progesterone, and HER-2 receptors that are the target of the most common and effective forms of therapy. Dr. Brown is studying transcription factors (molecules that turn genes on or off) that could be targeted for drug development to prevent or treat the spread of TNBC.
Current investigation: He and his team are studying a protein called SOX9 that regulates gene expression, which they found to be a “master regulator” of TNBC survival and metastasis. It controls the expression of genes that determine whether cancer cells invade through tissue and spread.
What he’s learned so far: Dr. Brown has shown that inhibition of SOX9 stops progression of metastatic disease in laboratory studies.
What’s next: He and his team plan to identify the proteins that activate SOX9 and the genes regulated by it that control tumor cell survival and spread. They will use this information to develop inhibitors of the SOX9 pathway and will determine whether targeting this pathway will effectively treat triple negative breast cancer in the laboratory.
Powel Brown is a medical oncologist and physician-scientist specializing in breast cancer treatment and prevention at the University of Texas, MD Anderson Cancer Center, where he is Chair of the Department of Clinical Cancer Prevention. He is conducting studies to identify novel targets for the treatment and prevention of breast cancer, particularly estrogen receptor (ER)-negative breast cancer. His team has conducted a BCRF-funded clinical trial of the kinase inhibitor lapatinib for the treatment of women with DCIS breast cancer. The results from this study will demonstrate whether lapatinib suppresses the growth of DCIS cells, and will be used to plan future DCIS breast cancer clinical trials to prevent the development of invasive breast cancer. Dr. Brown is also conducting preclinical studies of the signaling molecules in breast cancer with a particular focus on identifying the molecular drivers of "triple-negative" breast cancers. His research group has successfully identified several signaling pathways critical for breast cancer growth and development. Dr. Brown is also studying the death-associated protein kinase DAPK1, which his team has identified as one of the most highly expressed kinases in ER-negative breast cancer. This research will determine whether DAPK1 inhibitors suppress growth of p53-mutant breast cancer cells, the resistance pathways associated with DAPK1 inhibitors, and the ability of DAPK1 inhibitors to enhance the preventive effects of standard chemotherapeutic strategies. These studies will provide the foundation to target DAPK for the treatment of triple-negative breast cancers, the most aggressive form of breast cancer.