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 (panitumumab) and an immunotherapy agent (anti-PD-L1) for the treatment of these breast cancers. Dr. Ueno is also developing novel therapies to modulate the tumor microenvironment to prevent the spread of IBC cells 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 (the anti-PD1 antibody pembrolizumab) in patients with 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. 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.