{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:53:09Z","timestamp":1772164389421,"version":"3.50.1"},"reference-count":48,"publisher":"American Association for Cancer Research (AACR)","issue":"1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here, we report that the analysis of several large nonoverlapping cohorts of patients with medulloblastoma reveals MET kinase as a marker of sonic hedgehog (SHH)\u2013driven medulloblastoma. Immunohistochemical analysis of phosphorylated, active MET kinase in an independent patient cohort confirmed its correlation with increased tumor relapse and poor survival, suggesting that patients with SHH medulloblastoma may benefit from MET-targeted therapy. In support of this hypothesis, we found that the approved MET inhibitor foretinib could suppress MET activation, decrease tumor cell proliferation, and induce apoptosis in SHH medulloblastomas in vitro and in vivo. Foretinib penetrated the blood\u2013brain barrier and was effective in both the primary and metastatic tumor compartments. In established mouse xenograft or transgenic models of metastatic SHH medulloblastoma, foretinib administration reduced the growth of the primary tumor, decreased the incidence of metastases, and increased host survival. Taken together, our results provide a strong rationale to clinically evaluate foretinib as an effective therapy for patients with SHH-driven medulloblastoma. Cancer Res; 75(1); 134\u201346. \u00a92014 AACR.<\/jats:p>","DOI":"10.1158\/0008-5472.can-13-3629","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T01:08:12Z","timestamp":1415840892000},"page":"134-146","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma"],"prefix":"10.1158","volume":"75","author":[{"given":"Claudia C.","family":"Faria","sequence":"first","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"2Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon, Portugal."}]},{"given":"Brian J.","family":"Golbourn","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Adrian M.","family":"Dubuc","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Marc","family":"Remke","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Roberto J.","family":"Diaz","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Sameer","family":"Agnihotri","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Amanda","family":"Luck","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Nesrin","family":"Sabha","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Samantha","family":"Olsen","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Xiaochong","family":"Wu","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Livia","family":"Garzia","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Vijay","family":"Ramaswamy","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Stephen C.","family":"Mack","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Michael","family":"Leadley","sequence":"additional","affiliation":[{"name":"4Program in Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Denis","family":"Reynaud","sequence":"additional","affiliation":[{"name":"4Program in Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Leonardo","family":"Ermini","sequence":"additional","affiliation":[{"name":"4Program in Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Martin","family":"Post","sequence":"additional","affiliation":[{"name":"4Program in Physiology & Experimental Medicine, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Paul A.","family":"Northcott","sequence":"additional","affiliation":[{"name":"5Division of Pediatric Neurooncology and Division of Molecular Genetics, German Cancer Research Centre (DKFZ), University of Heidelberg, Heidelberg, Germany."}]},{"given":"Stefan M.","family":"Pfister","sequence":"additional","affiliation":[{"name":"5Division of Pediatric Neurooncology and Division of Molecular Genetics, German Cancer Research Centre (DKFZ), University of Heidelberg, Heidelberg, Germany."}]},{"given":"Sidney E.","family":"Croul","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Marcel","family":"Kool","sequence":"additional","affiliation":[{"name":"5Division of Pediatric Neurooncology and Division of Molecular Genetics, German Cancer Research Centre (DKFZ), University of Heidelberg, Heidelberg, Germany."}]},{"given":"Andrey","family":"Korshunov","sequence":"additional","affiliation":[{"name":"6Clinical Cooperation Unit Neuropathology, German Cancer Research Centre (DKFZ), Department of Neuropathology, University of Heidelberg, Heidelberg, Germany."}]},{"given":"Christian A.","family":"Smith","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."}]},{"given":"Michael D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"3Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada."},{"name":"7Division of Neurosurgery, Hospital for Sick Children, Toronto, Canada."}]},{"given":"James T.","family":"Rutka","sequence":"additional","affiliation":[{"name":"1Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Canada."},{"name":"7Division of Neurosurgery, Hospital for Sick Children, Toronto, Canada."},{"name":"8Department of Surgery, University of Toronto, Toronto, 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