Schwannomatosis is a rare genetic disorder that causes development of benign schwannomas in nerves, and intractable chronic pain. Mutations in two genes, SMARCB1 and LZTR1 are found in a subset of patients while the underlying cause remains unknown for the majority. There is a need for both non-surgical modalities to manage tumor growth and non-addictive pain control. This project is focused solely on tumor control. It uses a patient-derived schwannoma cell line to test the efficacy of candidate compounds in reducing viability of the cells in-vitro. Drug screens and target expression data showed that the JAK/STAT pathway participates in schwannoma growth. A small molecule JAK/STAT inhibitor (Compound X, CPD X) was found to reduce viability of the cells. CPD X decreased both cell viability and STAT-3 phosphorylation in a dose-dependent manner. Cell death studies showed that CPD X induces simultaneous caspase mediated apoptosis and necroptosis at a concentration of 3.0μM. The results of this study suggest CPD X may be a therapeutic compound for schwannomatosis related tumors and justifies further study in an in-vivo model.
Bachelor of Science (B.S.)
College of Medicine
Length of Campus-only Access
Allaf, Abdulrahman, "Identification of Druggable Targets in a Schwannomatosis Patient-Derived Tumor Cell Line" (2020). Honors Undergraduate Theses. 665.