DDDR-03. DRUG REPURPOSING VIA ULTRA-HIGH THROUGHPUT 3D SPHEROIDS SCREENING FOR HUMAN SCHWANNOMA

Abstract

Abstract Schwannoma is the most common benign peripheral nerve tumor occurring sporadically or as part of neurofibromatosis syndromes. While surgical resection can be used as the primary treatment option for Schwannoma, patients could face life-long repeated surgeries due to recurrence of syndromes that decreases the quality of life. Thus, non-invasive treatments for Schwannoma are highly demanded. To discover novel therapeutics for non-invasive Schwannoma treatment, in this project, we leveraged the benefits of drug repurposing high-throughput screening (HTS) of FDA-approved drugs using 3D spheroids derived from Schwannoma patient samples. Both 2D primary cells and 3D primary spheroids models were developed from an IRB-approved tumor bank of schwannoma patient samples. The 3D spheroids were validated to recapitulate the features of patient tumors. We then conducted an ultra-HTS(uHTS) in 1536-well format of 2036 FDA-approved drugs on the growth and viability of Schwannoma patient-derived 3D spheroids. Seven FDA-approved drugs were identified from the pilot screen to inhibit the growth of Schwannoma patient-derived 3D spheroids. These drugs offer potential to serve as pharmacotherapeutics for Schwannoma non-invasive treatment. Our results have demonstrated the capability of a drug repurposing strategy for Schwannoma using uHTS and a patient-derived tumor bank. We further demonstrated that patient-derived drug sensitivity signatures could be encoded from the screening data to enable clustering of patients, which accounts for heterogeneity in Schwannoma and avoids "one-size-fits-all" solutions in future non-invasive Schwannoma treatment studies.