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Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.
Children with Down syndrome (constitutive trisomy 21) that develop acute lymphoblastic leukemia (DS-ALL) have a 3-fold increased likelihood of treatment-related mortality coupled with a higher cumulative incidence of relapse, compared with other children with B-cell acute lymphoblastic leukemia (B-ALL).
Burn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes.
Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4, programmed cell death protein/ligand 1 are approved for treatment of multiple cancer types.
Nick Gottardo MBChB FRACP PhD Head of Paediatric and Adolescent Oncology and Haematology, Perth Children’s Hospital; Co-head, Brain Tumour Research
Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions.
Molecular 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.
Clinical management of breast cancer (BC) metastasis remains an unmet need as it accounts for 90% of BC-associated mortality. Although the luminal subtype, which represents >70% of BC cases, is generally associated with a favorable outcome, it is susceptible to metastatic relapse as late as 15 years after treatment discontinuation.
Cancer continues to be a leading cause of death globally. However, there remains a significant disparity in the reported incidence of cancer in developed countries, estimated to be 295.3 cases per 100,000 people, compared with only 115.7 in developing countries. Some of the reasons for this variation include lack of robust data collection with limited reporting systems, and insufficient data availability in the registries of these developing nations.
A review led by the First Nations Childhood Cancer team at The Kids Research Institute Australia has highlighted the urgent need for Indigenous-specific studies focused on cancer outcomes, survivorship and equity.