Blake Czapla
Pronouns: he/him
Research Mentor(s): Mukesh Nyati, Associate Professor
Research Mentor School/College/Department: Radiation Oncology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 6 (4pm-4:50pm)
Breakout Room: Room 13
Presenter: 2
Abstract
Glioblastoma multiforme (GBM) is one of the most aggressive forms of cancer which begins in the brain. In many GBM cases, there are mutations in Epidermal Growth Factor Receptor (EGFR), like EGFRvIII that is the most common variant. Currently, there are no treatments for GBM besides chemotherapy and surgery because a drug would need to cross the Blood-Brain Barrier (BBB) to target GBM. We have developed a novel small molecule, DPI503, that can cross the BBB, binds with EGFR, and promotes its degradation by blocking EGFR dimerization. Preliminary in vitro data show that DPI503 kills U87 glioblastoma cells stably transduced to express EGFRvIII with IC90 of 3 micro M. Therefore, we expect DPI503 to be effective against EGFRvIII expressing tumors. To test this, we will prepare an orthotopic brain tumor model by implanting luciferase-expressing U87-EGFRvIII tumor cells into the brains of SCID mice. The growth of the tumor will be monitored using an IVIS Lumina imaging system after intraperitoneal injection of Luciferin. After confirmation of established tumors, mice will be treated with 4 dose levels of DPI503 (0, 10, 30, 100 mg/kg) via daily oral gavage. We have found that DPI503 treatment is effective against EGFR driven HNSCC and lung flank xenograft model. We expect DPI503 to be effective against the GBM model as well. If single-agent activity is not curative, we would combine radiotherapy with DPI503 treatment in follow-up experiments.
Authors: Blake Czapla, Mukesh Nyati
Research Method: Laboratory Research with Animals
