Powel H. Brown, MD, PhD

Developing effective, targeted therapies for the prevention of triple-negative breast cancer

Impact

During the past ten years, incidence of breast cancer in the United States has steadily increased. Preventative drugs that target essential pathways involved in breast cancer development have been extensively studied. For example, endocrine therapies that target estrogen receptor (ER), can prevent the formation of ER-positive breast cancer. However, these therapies do not prevent the formation of ER-negative breast cancer. Because ER-negative breast cancers, including the aggressive triple-negative breast cancer (TNBC) subtype, are associated with poorer outcomes, there is a critical need to develop effective therapies that can prevent ER-negative and triple-negative breast cancer. Dr. Brown and his team are seeking to develop effective, targeted therapies that can prevent these subtypes of breast cancer.

Progress Thus Far

The team has found that the specific activator of retinoid X receptor (RXR), IRX4204, delays the formation of tumors in laboratory models of ER-negative and triple-negative breast cancer. IRX4204 can increase the presence of immune cells in triple-negative tumors, and treatment with targeted therapies, such as PARP inhibitors, checkpoint inhibitors, and mTOR inhibitors can delay but not prevent tumor formation in triple-negative models. The mechanism by which these drugs delay tumor formation is still unknown.

What’s next

The team will identify key molecules and pathways responsible for resistance to preventative agents in triple-negative tumor models and demonstrate that targeted therapies in combination with immune therapies can overcome tumor resistance and prevent tumor formation in laboratory models.