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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 aims to understand how genes that are essential for the survival of TNBC are regulated and how to effectively block them. Ultimately, his work could pave the way for novel therapeutic strategies for TNBC.
What’s next: He and his team are targeting proteins that regulate genes critical to TNBC survival with small molecule inhibitors. These could have the potential to become drugs 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, 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. He and his team have identified activators of SOX9 and genes regulated by SOX9.
What’s next: He and his team are targeting protein activators of SOX9 with small molecule inhibitors to block SOX9 activity and slow or prevent TNBC metastasis 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.