title: The therapeutic potential of targeting the PI3K pathway in pediatric brain tumors.
abstract: Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms. Pre-clinical analysis supports a role for PI3K signaling in the control of tumor growth, survival and migration as well as enhancing the cytotoxic effects of current treatments. Based on this evidence agents targeting PI3K signaling have begun to be tested in clinical trials of pediatric cancer patients. Overall, targeting the PI3K pathway presents as a promising strategy for the treatment of pediatric CNS tumors. In this review we examine the genetic alterations found in the PI3K pathway in pediatric CNS tumors and the pathological role it plays, as well as summarizing the current pre-clinical and clinical data supporting the use of PI3K pathway inhibitors for the treatment of these tumors.
authors.affiliation: Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Rogers
authors.affiliation: Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Jasper
authors.initials: J
authors.lastname: Estranero
authors.affiliation: Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Keshni
authors.initials: K
authors.lastname: Gudka
authors.affiliation: Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: PI3K pathway; brain tumor; cancer; pediatric; therapy