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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).
Impact: 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. His work will likely identify biomarkers for selecting IBC patients who will benefit from EGFR-targeted therapy and may also reveal molecules that can enhance the effectiveness of these drugs.
What’s next: Dr. Ueno and his team will use a novel technology to examine the changes in IBC cells after treatment with anti-EGFR therapy in combination with immunotherapy and identify biomarkers that can predict response to this combination therapy.
IBC is the most lethal and aggressive form of breast cancer and is typically a triple negative breast cancer. This presents a significant treatment challenge since hormone-targeted therapy is not helpful. Dr. Ueno is focusing on the cellular environment surrounding the tumor, called the tumor microenvironment, 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 goal: 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 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. Drugs that target the epidermal growth factor receptor (EGFR) have been shown to be effective in IBC patients. 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 IBCs. They are also developing novel therapies to modulate the TME to decrease tumor growth and reduce IBC patient death.
Current investigation: Utilizing a novel technology to identify proteins from patients’ tumor and blood samples that affect IBC response to EGFR-targeted therapy - this technology can then be applied in clinical trials to test the efficacy of panitumumab in combination with anti-PD-L1 immunotherapy in IBC patients.
What he’s learned so far: 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 tumor—called the tumor microenvironment (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 tumor microenvironment and reduced tumor growth in laboratory models. Panitumumab also increased the efficacy of immunotherapy.
What’s next: Dr. Ueno’s group is working to identify proteins from patients’ tumor and blood samples that can predict response to EGFR-targeted therapy. Use a specialized technology, called TGIRT-seq, they can monitor changes in key proteins in a series of 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 therapy for patients with IBC. Dr Ueno and his team hope to apply this technology in a clinical trial to test EGFR-targeted therapy in combination with anti-PD-L1 immunotherapy in patients with IBC.
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.