Rhea Raghavan
Research Mentor(s): Nathan Merrill
Mentor Department: Internal Medicine
Authors: Rhea Raghavan , Habib Serhan, Liwei Bao, Sofia Merajver , Aaron Udager , Nathan Merrill
Session: Session 6 (3:00pm – 3:50pm)
Presentation Type: Oral
Abstract
Sinonasal cancers are rare malignancies of the head and neck area, and while outcomes of other head and neck cancers have significantly improved, those of sinonasal cancers have remained fairly stable. This project focuses on inverted sinonasal papilloma (ISP) associated sinonasal squamous cell carcinoma (SNSCC), where it is noted that 50% of the ISPs that convert into malignancies have an epidermal growth factor receptor (EGFR) exon 20 mutation. These EGFR-mutated SNSCCs have a much worse prognosis than other sinonasal tumors and efforts are needed to develop more effective therapies. This study uses findings from a previous study conducted by Dr. Aaron Udager at the University of Michigan that found treatment of ISP-associated carcinoma cells with irreversible EGFR inhibitors resulted in inactivation of EGFR signaling and growth inhibition. In order to discover a synergistic pairing with optimal activity and reasonable pharmacokinetics, we used this basis to screen a library of >1000 inhibitors, calculated drug sensitivity scores (DSS3), and investigated the effectiveness in vitro using the Chou-Talalay method on four cell lines. Results suggest that SNSCC cell lines can be highly resistant and EGFR inhibition alone is not enough to sufficiently target cells. Bcl-2 inhibition shows significant synergistic anticancer potential in combination with EGFR inhibition in SNSCC, suggesting targeting anti-apoptotic pathways is important in enhancing EGFR inhibition. As the study progresses, mechanistic experiments will be performed to understand the relationship between EGFR and BCL-2, and optimal combinations will be chosen to test in vivo.
