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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
- Seeking to identify new targets for the treatment and prevention of breast cancer.
- New targeted therapies are tested in laboratory models of triple negative breast cancer (TNBC).
- While still early in development, these studies will enable development of novel therapeutic strategies to treat TNBC.
Triple negative breast cancer (TNBC) is aggressive form of the disease with a high likelihood of spreading to other tissues. Because TNBC cells lack the common therapeutic targets–estrogen receptor (ER) and HER2–it does not respond to ER- or HER2-targeted therapies. This leaves patients with few options outside of chemotherapy. Dr. Brown is conducting laboratory studies to uncover new targets for drug development to prevent or treat the spread of TNBC.
Full Research Summary
Dr. Brown and his team are investigating whether drugs that block specific cell signaling pathways are useful for the treatment and prevention of breast cancer. They are particularly interested in identifying new drug targets for the treatment of triple negative breast cancer (TNBC) and other estrogen receptor (ER)-negative breast cancers.
In previous analyses of gene expression in TNBC, his team identified 23 highly expressed transcription factors (molecules that turn genes on or off), including six that belong to the SOX family of transcription factors.
Over the last year, Dr. Brown’s team discovered that SOX9 is a “master regulator” of triple-negative breast cancer survival and metastasis. This protein controls the expression of genes that determine whether cancer cells invade through tissue and metastasize. In laboratory experiments, inhibition of SOX9 caused triple negative breast cancer cells to die and inhibited the growth of breast cancer metastases.
Over the next year, they will screen for drugs and combination approaches that can inhibit SOX9.
These studies will fuel the development of novel therapeutic strategies to treat or prevent TNBC metastasis.
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.
BCRF Investigator Since