Abstract 5402: Inhibition of RET via BLU-667 in anin vitromodel of neuroblastoma

Neuroblastoma is the most common extracranial solid tumor of childhood. Despite aggressive treatment, outcomes in patients with high-risk disease remains poor and new therapeutics are needed to address their needs. Rearranged during Transfection (RET) is a tyrosine kinase that is a known oncogenic driver of multiple human tumors. RET is expressed on neural crest derived cells, including neuroblastoma cells, and has been shown to play a role in neuroblastoma proliferation and survival as well. Recent studies have shown RET inhibition to be a promising new therapeutic target in neuroblastoma. BLU-667 is a selective RET inhibitor with a higher potency and specificity for RET than the current inhibitors that have been previously tested. We hypothesize that this increased potency and specificity will result in greater efficacy against neuroblastoma in preclinical models with fewer off target effects. Thus, to investigate this we evaluated BLU-667 at different concentrations against a panel of established human neuroblastoma cell lines to assess its effects on neuroblastoma cell proliferation, differentiation, and viability. We found that inhibition of RET resulted in a significant decrease in cell proliferation and viability in vitro. Further, given the increased specificity of BLU-667 to RET, we hope to use western blot protein analysis to establish the specific downstream pathways through which RET inhibition leads to decreased neuroblastoma cell survival, potentially revealing further therapeutic targets. Citation Format: Jessica Gutierrez, Sean Flynn, Yuchen Huo, Jacqueline Lesperance, Peter Zage. Inhibition of RET via BLU-667 in an in vitro model of neuroblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5402.