EXTH-59. IDENTIFICATION OF GROWTH HORMONE RECEPTOR AS A RELEVANT TARGET FOR PRECISION MEDICINE IN LOW-EGFR EXPRESSING GLIOBLASTOMA

Abstract

Abstract New therapeutic approaches are needed to improve the prognosis of Glioblastoma (GBM) patients. With the objective of identifying alternative oncogenic mechanisms to abnormally activated EGFR signaling, one of the most common oncogenic mechanisms in GBM, we performed a comparative analysis of gene expression profiles in a series of 54 human GBM samples. We identified that Growth Hormone Receptor (GHR) signaling defines a distinct molecular subset of GBMs devoid of EGFR overexpression. GHR overexpression was detected in one third of patients and was associated with low levels of SOCS2 expression due to SOCS2 promoter hypermethylation. In GBM patient-derived cell lines, GHR signaling modulates the expression of proteins involved in cellular movement, promotes cell migration, invasion and proliferation in vitro, and promotes tumorigenesis, tumor growth and tumor invasion in vivo. GHR genetic and pharmacological inhibition reduced cell proliferation and migration in vitro. GHR signaling pathway thus emerges as an oncogenic signaling pathway in low EGFR-expressing GBMs and as a promising therapeutic target. This study pioneers a new field of investigation to improve the prognosis of GBM patients.