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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.
OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies to target this tumor cell population.
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.
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.
Acute lymphoblastic leukaemia is the most common childhood malignancy that remains a leading cause of death in childhood. It may be characterised by multiple known recurrent genetic aberrations that inform prognosis, the most common being hyperdiploidy.
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-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.
Britta Regli-von Ungern-Sternberg AM FAHMS MD, PhD, DEAA, FANZA Chair of Paediatric anaesthesia, University of Western Australia; Consultant
Honorary Research Associate
Feilman Fellow; Head, Precision Health Research and Head, Translational Intelligence