IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.
作者： Matthew N. Svalina , Ken Kikuchi , Jinu Abraham , Sangeet Lal , Monika A. Davare
DOI: 10.1038/SREP27012
关键词:
摘要: Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison cytokines growth factors cerebrospinal fluid (CSF) metastatic patients with also conditioned media MYC amplified leptomeningeal cells, we were led to explore bioactivity IGF1 by elevated CSF levels IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP tPA), protease modulators (TIMP1 PAI-1). not only receptor phosphorylation but accelerated migration/adhesion cells context appropriate matrix meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source IGF-liberating that could facilitate metastasis. In parallel, studies key responsible for cell autonomous prioritized IGF1R inhibitors. Together, our identify as high value target clinical trials risk medulloblastoma.
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