The lancet oncology
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Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signalling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumour suppressors is often required for development of cancer. ⋯ Preclinical studies show that pharmacological restoration of PP2A tumour-suppressor activity by PP2A-activating drugs (eg, FTY720) effectively antagonises cancer development and progression. Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols.
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The lancet oncology · May 2013
Multicenter StudySafety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study.
Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. ⋯ Pfizer and National Cancer Institute grant to the Children's Oncology Group.
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The lancet oncology · May 2013
Multicenter StudyMethylation of the TERT promoter and risk stratification of childhood brain tumours: an integrative genomic and molecular study.
Identification of robust biomarkers of malignancy and methods to establish disease progression is a major goal in paediatric neuro-oncology. We investigated whether methylation of the TERT promoter can be a biomarker for malignancy and patient outcome in paediatric brain tumours. ⋯ The Canadian Institute of Health Research and the Terry Fox Foundation.