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RaScALL: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early.
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ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline GliomaDiffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9 to 11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG.
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A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancerMolecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers.
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Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour ImmunosuppressionImmunotherapy has revolutionised the treatment of cancers by harnessing the power of the immune system to eradicate malignant tissue. However, it is well recognised that some cancers are highly resistant to these therapies, which is in part attributed to the immunosuppressive landscape of the tumour microenvironment (TME). The contexture of the TME is highly heterogeneous and contains a complex architecture of immune, stromal, vascular and tumour cells in addition to acellular components such as the extracellular matrix. While understanding the dynamics of the TME has been instrumental in predicting durable responses to immunotherapy and developing new treatment strategies, recent evidence challenges the fundamental paradigms of how tumours can effectively subvert immunosurveillance. Here, we discuss the various immunosuppressive features of the TME and how fine-tuning these mechanisms, rather than ablating them completely, may result in a more comprehensive and balanced anti-tumour response.
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Malignant Melanoma in Children and Adolescents Treated in Pediatric Oncology Centers: An Australian and New Zealand Children’s Oncology Group (ANZCHOG) StudyUnlike adults, malignant melanoma in children and adolescents is rare. In adult melanoma, significant progress in understanding tumor biology and new treatments, including targeted therapies and immunotherapy have markedly improved overall survival. In sharp contrast, there is a paucity of data on the biology and clinical behavior of pediatric melanoma. We report a national case series of all pediatric and adolescent malignant melanoma presenting to ANZCHOG Childhood Cancer Centers in Australia and New Zealand.
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Parental occupational exposure to pesticides and risk of childhood cancer in Switzerland: a census-based cohort studyPesticide exposure is a suspected risk factor for childhood cancer. We investigated the risk of developing childhood cancer in relation to parental occupational exposure to pesticides in Switzerland for the period 1990-2015.
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Tumor Infiltrating Effector Memory Antigen-Specific CD8(+) T Cells Predict Response to Immune Checkpoint TherapyImmune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT.
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What matters for people with brain cancer? Selecting clinical quality indicators for an Australian Brain Cancer RegistryThe goal of a clinical quality registry is to deliver immediate gains in survival and quality of life by delivering timely feedback to practitioners, thereby ensuring every patient receives the best existing treatment. We are developing an Australian Brain Cancer Registry (ABCR) to identify, describe, and measure the impact of the variation and gaps in brain cancer care from the time of diagnosis to the end of life.
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Cancer therapies inducing DNA damageThe induction of DNA damage has been employed as an anticancer strategy for more than 100years, first starting with the use of radiation to treat stomach cancer followed by the first uses of DNA-damaging chemotherapy to treat childhood leukemia.
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Systematic In Vitro Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged LeukemiaPatients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics.