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The Kids Research Institute Australia Cancer Researcher recognised in 2021 Business Events Perth Aspire AwardsOne of The Kids Research Institute Australia’s leading young researchers will travel to the world’s premier conference on childhood brain cancer.
Research
Celebrating 100 years of Immunology & Cell Biology – a special focus on the field of tumor immunology in AustraliaIn this Commentary article, as part of the 100-year celebrations of the journal, we reflect on the contribution of articles published in ICB in the field of tumor immunology. A highlight is a series of interviews conducted with three Australian-based ICB authors who have contributed key papers over the years: Rajiv Khanna, Delia Nelson and Ian Frazer.
Research
Improving compliance with swallowing exercise to decrease radiotherapy-related dysphagia in patients with head and neck cancerDysphagia, one of the most common complications in head and neck cancer (HNC) treated with radiotherapy, can severely affect patients’ quality of life. Currently, because no “gold standard” treatment exists, swallowing exercise remains the main rehabilitation strategy for dysphagia. However, patients’ compliance with long-term swallowing exercise is only 40%, thus, greatly compromising outcomes. This article aims to analyze thefactors influencing swallowing exercise compliance in patients with HNC and explains strategies developed to date for improved rehabilitation outcomes.
Research
Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive CombinationsAntibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA‐4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB.
Research
Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint TherapyWith immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity.
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A surveillance clinic for children and adolescents with, or at risk of, hereditary cancer predisposition syndromesHereditary cancer predisposition syndromes (HCPS) account for at least 10% of paediatric cancers.1 Li‐Fraumeni syndrome (LFS) is a dominant HCPS caused by mutations in the TP53 gene and is associated with an 80–90% lifetime risk of cancer, commencing in infancy.2 Children of affected individuals are at 50% risk of inheriting the family mutation.
Research
Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancerThe Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations.
Research
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.
Research
Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell LeukemiaChildren 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).
Research
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.