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A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain TumorsGlioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors.
Research
Small-molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastomaMedulloblastoma (MB) consists of four core molecular subgroups with distinct clinical features and prognoses. Treatment consists of surgery, followed by radiotherapy and cytotoxic chemotherapy. Despite this intensive approach, outcome remains dismal for patients with certain subtypes of MB, namely, MYC-amplified Group 3 and TP53-mutated SHH. Using high-throughput assays, six human MB cell lines were screened against a library of 3208 unique compounds. We identified 45 effective compounds from the screen and found that cell cycle checkpoint kinase (CHK1/2) inhibition synergistically enhanced the cytotoxic activity of clinically used chemotherapeutics cyclophosphamide, cisplatin, and gemcitabine.
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RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational StatusPTEN mutation occurs in a variety of aggressive cancers and is associated with poor patient outcomes. Recent studies have linked mutational loss of PTEN to reduced RAD51 expression and function, a key factor involved in the homologous recombination (HR) pathway. However, these studies remain controversial, as they fail to establish a definitive causal link to RAD51 expression that is PTEN-dependent, while other studies have not been able to recapitulate the relationship between the PTEN expression and the RAD51/HR function.
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Developing new immune based therapies for neuroblastomaNeuroblastoma is a complex childhood cancer of the nerve cells and the most common solid tumour in children outside of the brain. The average age of diagnosis is 1-2 years and tragically 50% of children with high-risk neuroblastoma lose their battle within five years.
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Finding new, safer and targeted therapies for paediatric brain cancer that amplify responses to radiation therapyRadiation therapy is an essential component of brain cancer treatment. However, the high doses currently required are extremely damaging to the growing brains and bodies of children.
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Recurrent MET fusion genes represent a drug target in pediatric glioblastomaWe identified previously unidentified gene fusions involving the MET oncogene in pediatric glioblastoma
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Relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated without irradiationThis study investigated the relapse and outcome patterns of patients with central nervous system mixed malignant germ cell tumors treated with chemotherapy-only
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Efficacy of acute myeloid leukemia therapy without stem-cell transplantation in a child with blastic plasmacytoid dendritic cell neoplasmOur case demonstrates that AML therapy, without HSCT, can be sufficient to treat this rare disease in children.
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Glioma-specific Domain IV EGFR cysteine mutations promote ligand-induced covalent receptor dimerization and display enhanced sensitivityEpidermal growth factor receptor (EGFR) is over-expressed in many brain tumors. This paper examines mutations the EGFR that make the cell it is produced in...
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The evolution of clinical trials for infant acute lymphoblastic leukemiaDespite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has...