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Naoto T. Ueno, MD, PhD
Professor of Medicine
The University of Texas MD Anderson Cancer Center
Goal: To develop novel therapies that will improve outcomes for patients with inflammatory breast cancer (IBC), a rare and very aggressive disease in which cancer cells infiltrate the skin and lymph vessels of the breast.
Impact: Dr. Ueno and his team showed that a drug targeting the epidermal growth factor receptor (EGFR) could induce immune cells to penetrate IBC tumors and kill tumor cells. Dr. Ueno’s work will likely identify biomarkers for selecting IBC patients who will benefit from EGFR-targeted therapy and may also reveal molecules that can enhance these drugs’ effectiveness.
What’s next: Dr. Ueno and his team will use a novel technology to examine the changes IBC cells after treatment with anti-EGFR therapy to help predict response to the therapy. They also plan to establish an experimental model to accurately evaluate the efficacy of anti-tumor drugs.
IBC is the most lethal and aggressive form of breast cancer, and it’s also challenging to treat because the tumors usually lack hormone receptors, which means hormone therapy drugs aren’t helpful. Dr. Ueno is focusing on the cellular environment surrounding the tumor, called the tumor microenvironment (TME), which has been shown to promote IBC tumor growth. He hopes to develop a novel therapy that regulates the tumor microenvironment, which could reduce the risk of death in IBC patients.
Full Research Summary
Research area: To reduce patient death from inflammatory breast cancer (IBC) by developing a novel therapy that modulates the network of cells and structures that surround a tumor (the tumor microenvironment).
Impact: IBC is the most lethal and aggressive form of breast cancer, and it 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 is investigating the microenvironment of IBC tumors—which contains cells and tissue that can either promote or inhibit tumor development—to identify potential targets for treatment.
Current research: He and his colleagues have been studying a type of treatment that targets the epidermal growth factor receptor (EGFR) that, when combined with preoperative chemotherapy, has a high rate of tumor response in patients with primary IBC. Their work will likely identify predictive biomarkers for selecting IBC patients who will benefit from EGFR-targeted therapy and may also lead to the identification of novel molecules that can enhance the therapeutic efficacy of EGFR-targeted therapy for patients with IBC.
What he’s learned so far: Dr. Ueno has shown in laboratory models that anti-EGFR antibody panitumumab (PmAb) may induce immune cells to penetrate IBC tumors and kill tumor cells. He and his team have also demonstrated the role of a type of immune cell called a mast cell in response of IBC patients to preoperative chemotherapy and identified cytokines that may regulate PmAb immune response in IBC.
What’s next: The team will use a novel technology, single-cell RNA sequencing, to examine the change of each cell in IBC patients and laboratory tissues after treatment with PmAb. This will give the most accurate information on panitumumab’s impact on the IBC tumor microenvironment. In addition, they plan to develop a laboratory model that will grow tumors with the clinical characteristics of IBC, which will allow them to evaluate the efficacy of anti-tumor drugs.
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.