Lori J. Pierce, MD, FASCO, FASTRO

Identifying ways to enhance the effectiveness of radiation in women with aggressive forms of breast cancer.

Impact

Despite treatment that includes radiation therapy, many women with aggressive forms of breast cancer will experience a recurrence in the breast. Dr. Pierce has been focused on the causes of radio-resistance in breast cancer and developing radio-sensitization strategies for treating patients. With BCRF support, she has focused on combining radiation with other therapies to treat breast cancer and has shown that different drugs can indeed make radiation more effective. In laboratory studies, Dr. Pierce’s team has shown increased cancer cell death with radiation and hormonal therapy targeting the androgen- and estrogen-receptors whereby the combination acts on the tumor’s cell cycle machinery. These studies have also demonstrated that combination therapy also increases the immune response which has the potential to further reduce tumor growth. Dr. Pierce and her colleagues are now conducting similar studies to increase the effectiveness of radiation therapy for treating other aggressive forms of breast cancer, such as triple-negative breast cancer (TNBC).

Progress Thus Far

In the last year, Dr. Pierce focused on two important protein targets in TNBC that both influence cancer cell growth and are critical in cell division, monopolar spindle kinase 1 (TTK) and Aurora kinase B (AURKB). Prior research by her group and others suggested that activity of both proteins is increased in patients with solid tumors including TNBC. Further, Dr. Pierce’s team found that TTK expression is associated with in-breast cancer recurrence in patients who had received radiotherapy. Using well-established TNBC cellular models, they found that TTK/AURKB inhibitors made TNBC cells more sensitive to radiotherapy. Next, they used laboratory models to examine the effect of the combination on immune-mediated anti-tumor signaling and demonstrated that TTK inhibition plus radiotherapy controls tumor growth, suggesting that inhibiting this protein can make TNBC cells more sensitive to radiotherapy.

What’s next

In the next year, Dr. Pierce will build on these findings to test the combination of radiation plus cell cycle-targeted therapy and immunotherapy in the TNBC models. In other studies, her team will study potential differences in the radiation sensitivity between invasive lobular and invasive ductal cancers which recently were found to have distinct differences in histology as well as molecular and genetic markers. Invasive lobular cancers are also associated with a higher rate of nodal involvement, higher rates of distant spread, and are less responsive to chemotherapy compared to invasive ductal cancers. They are testing whether lobular cancers are more sensitive to radiation compared to the ductal subtype. Dr. Pierce’s ultimate goal for this line of research is to identify potential opportunities to reduce the radiation dose required to treat women with infiltrating lobular cancers, potentially decreasing toxicities experienced with radiation treatment. Collectively, these studies may have important implications for translation into the clinic.

Read more about Dr. Pierce’s work as part of BCRF’s Health Equity Initiative here.