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BCRF Grantee Since

2004

Donor Recognition

The J.C. Penney Award

Area(s) of Focus

Powel H. Brown, MD, PhD

John Charles Cain Distinguished Chair
Chair and Professor
Department of Clinical Cancer Prevention
University of Texas MD Anderson Cancer Center
Houston, Texas

Current Research

Estrogen receptor-positive (ER+) breast cancers are typically treated with anti-estrogen drugs, which have significantly improved the success of treating and preventing many cases of invasive breast cancer. However, estrogen receptor-negative (ER-) breast cancers, and particularly the aggressive triple negative breast cancers, which represent about 20% of cases, are unresponsive to anti-estrogen drugs and do not effectively respond to current chemotherapeutic strategies, which themselves subject the patient to significant toxicity. Thus, there is an urgent need to identify molecules critical for cellular growth and tumor formation (tumorigenesis) in order to develop effective, non-toxic, targeted therapies for treatment of women with ER- breast cancers.

Dr. Brown’s team has investigated whether signal transduction inhibitors are useful for the treatment and prevention of breast cancer. These researchers are conducting studies of breast tumors to identify novel targets for the treatment of ER- breast cancer. They have previously identified several signaling molecules that are highly expressed in human ER- breast cancers that are potential targets for treatment. One of their aims in 2013-2014 is to conduct a clinical trial to target the HER2 and EGFR growth factor receptor kinases in women with HER2-positive or EGFR-positive DCIS breast cancer. This ongoing study, supported by funds from BCRF, is currently open at the University of Texas MD Anderson Cancer Center, as well as Dana-Farber Cancer Institute, the Mayo Clinic, and the University of Alabama. This clinical trial will help determine whether the drug lapatinib will be useful for the treatment of HER2-positive or EGFR-positive DCIS breast cancer. Other goals of Dr. Brown’s research include testing whether another kinase, the signaling molecule MAP3K12, will be a useful target for the treatment of triple negative breast cancers. These breast cancers do not express the estrogen receptor, the progesterone receptor, or HER2 protein. No effective targeted therapy is available for these particularly aggressive tumors and Dr. Brown’s study will help determine whether drugs targeted to the MAP3K12 kinase could be used to treat triple negative breast cancers in the future. The study will provide the scientific rationale necessary for the development of molecularly-targeted therapeutic strategies allowing for personalized treatment regimens for women with ER-negative breast cancer.

Mid-Year Summary

Dr. Brown and his team have investigated whether signal transduction inhibitors are useful for the treatment and prevention of breast cancer. These researchers are conducting studies of human breast tumors to identify novel targets for the treatment of estrogen receptor (ER)-negative breast cancer. They have previously identified several signaling molecules that are highly expressed in human ER-negative breast cancers that are potential targets for treatment. In Aim 1, Dr. Brown and his collaborators are conducting a clinical trial to target the HER2 and EGFR growth factor receptor kinases in women with HER2-positive or EGFR-positive DCIS breast cancer. This study, supported by BCRF, is currently open at the Mayo Clinic, the University of Alabama, and MD Anderson Cancer Center, and will determine whether the drug lapatinib will be useful for the treatment of Her2-positive or EGFR-positive DCIS breast cancer. In Aims 2 and 3, Dr. Brown and his laboratory team are testing whether another kinase, the signaling molecule MAP3K12, will be a useful target for the treatment of “triple-negative breast cancers”. These triple-negative breast cancers do not express the estrogen receptor, the progesterone receptor, or HER2 protein. No effective targeted therapy is available for these particularly aggressive tumors and this study will help determine whether drugs targeted to the MAP3K12 kinase could be used to treat triple-negative breast cancers in the future. The laboratory-based studies have demonstrated that inhibition of MAP3K12 downregulates the cell cycle and upregulates cell death (apoptosis) in triple-negative breast cancer cells. These studies lay the foundation for targeting MAP3K12 for the treatment of breast cancer.

Bio

Dr. 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 serves as Professor and Chair of the Department of Clinical Cancer Prevention. Dr. Brown leads the Cancer Prevention program and his laboratory and clinical efforts are focused on developing more effective ways to treat and prevent breast cancer. Dr. Brown is leading the LAPIS clinical trial, a multicenter neoadjuvant trial of lapatinib for the treatment of women with DCIS breast cancer, supported by BCRF. The results from this study will demonstrate whether lapatinib suppresses breast cell proliferation in women with DCIS. These results will be used to plan future DCIS breast cancer clinical trials in which lapatinib will be given to women in an attempt to prevent the development of invasive breast cancer. The lapatinib trial will provide essential information to develop future breast cancer prevention drugs. Such an advance will potentially have a major impact on the public health of women worldwide.

The focus of his Dr. Brown's current laboratory research is to identify critical drivers of breast tumor development that can be targeted for more effective treatment and prevention of “triple-negative” breast cancer. In his ongoing BCRF project, his team of investigators is investigating whether specific signaling molecules (MAP3Ks) can be targeted for treatment of triple-negative breast cancer. Dr. Brown also directs an NCI-funded multi-center clinical trial consortium through which early phase cancer prevention trials are conducted. Through these studies, Dr. Brown is identifying early drivers of breast oncogenesis and testing new strategies to treat and prevent cancer.

Dr. Brown is discovering how growth factors and hormones induce changes in gene expression that lead to the development of breast cancer. He has successfully identified several signaling pathways that are critical for breast cancer development.