Powel H. Brown, MD, PhD

Developing effective, targeted therapies for the prevention of BRCA1 mutant breast cancer

Impact

Women carrying a BRCA1 gene mutation are at greater risk for developing breast cancer, often at a younger age with more aggressive tumors that result in a poor prognosis and decreased life expectancy. Currently, the only effective prevention option for these women is a highly invasive and irreversible surgical procedure to completely remove the breast tissue. Dr. Brown and his team seek to identify novel lipid molecules important for the activation of anti-tumor immune cells that play a role in the suppression of breast tumor formation. They will also demonstrate the preventive efficacy of targeted therapies combined with immune therapies, with the hopes that the findings will ultimately lead to effective prevention of BRCA1 mutant breast cancer.

What’s next

The long-term goal of the research is to develop safe and effective therapies that prevent the development of breast cancer in women with inherited BRCA1 mutations. Inhibitors of poly ADP-ribose polymerase (PARP), an FDA approved targeted therapy for BRCA1-deficient tumors, have been found to modestly delay the formation of tumors in relevant laboratory models. However, these treatments are associated with toxicities that limit their use for prevention. Activators of the retinoid X receptor (RXR) have been shown to inhibit the growth of breast cancer, alter the immune system, and are less toxic than current breast cancer therapies. It is known that lipid molecules can stimulate an immune response, and the team hypothesizes that the preventative effect of the RXR activator is partially due to the release of lipid molecules that can activate the local immune system and delay the formation of tumors. The team will proceed with identifying the lipid molecules important for the activation of anti-tumor immune cells and define the specific immune players involved in the prevention of mutant breast cancer upon treatment with the RXR activator or a PARP inhibitor. They will also determine whether the combination of immune and RXR activator therapies will effectively prevent the development of tumors in their laboratory models.