Rhea Raghavan
Pronouns: she/her
Research Mentor(s): Nathan Merrill
Research Mentor School/College/Department: Internal Medicine / Medicine
Program:
Authors: Rhea Raghavan , Habib Serhan , Hamadi Madhi , Liwei Bao , Sofia Merajver , Nathan Merrill
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 46
Abstract
Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer and contributes significantly to overall breast cancer-related mortality. It is characterized by inflammation and swelling of the affected breast due to the obstruction of dermal lymphatics. Because IBC is not resectable at initial diagnosis, current standard treatment for IBC involves trimodality therapy consisting of neoadjuvant therapy, surgery, and then radiation. However, the prognosis for IBC remains worse than in other non-inflammatory locally advanced breast cancers, and efforts are needed to develop more effective systemic therapies to improve treatments for these patients. We previously screened a library of 1300 compounds on over 20 breast cancer cell lines, and noted that IBC cell lines are more sensitive to heat shock protein 90 (HSP90) and Bcl-2 family inhibitors. This study examines the effectiveness of existing IBC drug therapies in combination with the HSP90 inhibitor pimitespib and Bcl-2 inhibitor navitoclax. In order to discover synergistic effects of pimitespib and navitoclax with other drugs, we screened the same library of 1300 compounds on various IBC cell lines once in the presence and absence of pimitespib or navitoclax. We plotted dose-response curves and then calculated drug sensitivity scores (DSS3) using R software to compare the results. Compounds that showed improvement in activity with pimitespib and navitoclax were further investigated as potential companion drugs in the lab using the Chou-Talalay method. Results suggest pimitespib has significant synergistic anticancer potential in IBC, specifically in combination with taxanes and PI3K and MAPK pathway inhibitors. Navitoclax shows significant promise in combination with a MEK inhibitor. As the study progresses, we will choose the optimal combination to test in vivo.
