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Preclinical Assessment of Dactinomycin in KMT2A-Rearranged Infant Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have high rates of relapse and poor survival compared with children. Few new therapies have been identified over the past twenty years. The aim of this study was to identify existing anti-cancer agents that have the potential to be repurposed for the treatment of infant ALL.

Imaging of Abdominal Complications in Children With Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and remains one of the most common causes of cancer-related death in children and adolescents. Five-year overall survival rates now exceed 90% with current multidrug chemotherapeutic regimens.

Polyamine depletion limits progression of acute leukaemia

Cancer cells are addicted to polyamines, polycations essential for cellular function. While dual targeting of cellular polyamine biosynthesis and polyamine uptake is under clinical investigation in solid cancers, preclinical and clinical studies into its potential in haematological malignancies are lacking. Here we investigated the preclinical efficacy of polyamine depletion in acute leukaemia.

Determining risk features for medulloblastoma in the molecular era

Nick Gottardo MBChB FRACP PhD Head of Paediatric and Adolescent Oncology and Haematology, Perth Children’s Hospital; Co-head, Brain Tumour Research

Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy

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.

Pharmacological targeting and characterization of Voltage-Gated Sodium Channels (VGSCs) expressed in the high-grade glioma microenvironment

High-grade glioma (HGG) cells reactivate neurodevelopmental programs regulated by ion channels to drive tumor progression. The activity of voltage-gated sodium channels (VGSCs) is fundamental to development, a target of blood-brain barrier (BBB)-permeable FDA-approved drugs, and aids tumor advancement in several cancers. However, the contribution of VGSC activity to HGG pathology remains unknown.

Skeletal muscle health in childhood cancer survivors: a systematic review and meta-analysis

Childhood cancer survivors (CCS) are at risk of long-term skeletal muscle deficits following intensive therapies during critical periods of growth. This review aimed to synthesize approaches for assessing muscle quantity, quality, and function in CCS and to quantify deficits relative to healthy peers. 

Age-based pegaspargase dosing is safe and achieves therapeutic levels in infants with ALL: report from COG AALL15P1

Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia

CAR T cells targeting B7H3 demonstrate potent preclinical activity against AML and ESCC

T cells engineered to express chimeric antigen receptors (CARs) are a promising modality to treat refractory cancers. CD19 CAR-T therapy has achieved remarkable responses in against B-cell lymphomas, however, challenges persist for acute myeloid leukemia (AML) and solid malignancies. B7H3 is an immune regulatory molecule that is highly expressed in various tumor cells. Its abnormal expression in acute AML and esophageal squamous cell carcinoma (ESCC) is closely related to tumor progression. 

High Expression of NTRK1 in ETV6::RUNX1 Positive Acute Lymphoblastic Leukaemia Drives Factor Independence and Sensitivity to Larotrectinib

ETV6::RUNX1 is one of the most common recurrent genomic abnormalities in acute lymphoblastic leukaemia (ALL) and is associated with a good prognosis. High expression of NTRK1, encoding tropomyosin receptor kinase A (TrkA), confers a poor prognosis in other malignancies and may contribute to therapy resistance in patients with ETV6::RUNX1 B-ALL.