Naoto T. Ueno, MD, PhD

Developing novel therapies that will improve outcomes for patients with inflammatory breast cancer, a rare and very aggressive form of the disease.

Impact

Inflammatory breast cancer (IBC) is the most lethal and aggressive form of breast cancer, likely to be triple-negative (lacking hormone and HER2 receptors), and with 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 cell-surface protein called EGFR could improve response to immunotherapy in laboratory models of IBC. His team is investigating the effectiveness of combining EGFR-targeted therapy with immunotherapy for the treatment of these breast cancers. Dr. Ueno is also developing novel therapies to prevent the spread of IBC to the skin and lymph vessels surrounding the breast. He hopes to identify biomarkers for selecting IBC patients who will benefit from EGFR-targeted therapy and strategies to enhance the effectiveness of these drugs and ultimately improve outcomes for patients.

Progress Thus Far

Using technologies that identify single cells, his team has analyzed changes in the cellular composition of the tumor microenvironment after EGFR-targeted treatment. Their laboratory studies have shown that an anti-EGFR drug called panitumumab increased the infiltration of immune cells into the microenvironment and tumor, effectively reducing tumor growth. A clinical trial is underway to test panitumumab with an immunotherapy agent (pembrolizumab) in patients with IBC. Dr. Ueno and his colleagues continue to screen compounds that can inhibit the activity of EGR1 in IBC. They have identified another target called TBK1 in triple negative breast cancer and will continue to explore its function and relevance in IBC.

What’s next

Dr. Ueno’s group will continue to explore the mechanism of action of panitumumab in modulating the TME in IBC tumors while they expedite the development of EGR1-targeted therapy. They will leverage a new drug targeting technology that works by degrading the targeted protein of interest. They will explore how their EGFR1 degraders affect the growth of IBC cells and movement of immune cells to IBC tumor. His team will continue their work in TBK1 to understand its effect on the TME and anti-tumor immune response. In aggregate, Dr. Ueno’s studies address the urgent need to develop novel and effective therapies for IBC and improve the efficacy of immunotherapy for patients with IBC.