Naoto T. Ueno, MD, PhD
Professor of Medicine
The University of Texas MD Anderson Cancer Center
Developing novel therapies that will improve outcomes for patients with inflammatory breast cancer, a rare and very aggressive form of the disease.
Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer. It is typically triple-negative (lacking hormone and HER2 receptors) and has a high rate of metastasis. Although the disease affects only two to four percent of breast cancer patients, it is responsible for about 10 percent of breast cancer deaths in the United States. Thus, new treatment strategies to reduce IBC recurrence and metastasis are urgently needed. Dr. Ueno and his team showed that a drug targeting the epidermal growth factor receptor (EGFR) could induce immune cells to penetrate and kill IBC tumor cells. Dr. Ueno and his team are investigating the effectiveness of combining EGFR-targeted therapy (panitumumab) and an immunotherapy agent (anti-PD-L1) for the treatment of these breast cancers. Based on the finding that IBC cells can infiltrate the skin and lymph vessels of the breast and the tumor microenvironment (TME)—the tissue and cells that surround the tumor—Dr. Ueno is also developing novel therapies to modulate the TME to decrease tumor growth. His work will likely identify biomarkers for selecting IBC patients who will benefit from EGFR-targeted therapy and may also reveal strategies to enhance the effectiveness of these drugs and ultimately improve outcomes for patients.
Dr. Ueno has established that the EGFR pathway is a valid therapeutic target in IBC. Using technologies that identify single cells, his team has analyzed changes in the cellular landscape surrounding the TME after EGFR-targeted treatment. Their studies have shown that an anti-EGFR drug called panitumumab increased the number of immune cells in the IBC TME, induced these immune cells to penetrate the tumors, and reduced tumor growth in laboratory models. The team showed that panitumumab also increased the efficacy of immunotherapy, by blocking the production of a tumor promoting protein called CCL2.
Dr. Ueno's group will continue to explore the role of CCL2 in modulating the TME in IBC tumors. They will also utilize a specialized technology to monitor changes in key proteins from patient blood samples obtained over the course of treatment. They hope these studies will lead to the identification of new molecules that can enhance the efficacy of EGFR-targeted treatment.
Naoto T. Ueno is a Professor of Medicine at The University of Texas MD Anderson Cancer Center; his research is in the area of inflammatory breast cancer/triple negative breast cancer, the molecular mechanism of metastasis (cancer microenvironment), and tumorigenicity in breast cancer. He is best known for his preclinical development for E1A, EGFR, HER2, MAPK pathway targeting therapy leading to novel clinical trials related. He is the Executive Director of the Morgan Welch Inflammatory Breast Cancer Program and Clinic and Section Chief of the Translational Breast Cancer Research at Department of Breast Medical Oncology.
He is passionate about education related to clinical/translational research. He received The University of Texas System Regents’ Outstanding Teaching Award in 2013. Dr. Ueno received the Nylene Eckles Distinguished Professorship of Breast Cancer Research in 2012. He also received MD Anderson Distinguished Clinical Faculty Mentor Award in 2019.
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