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Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179

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.

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 inhibition of sclerostin protects bone from B-cell acute lymphoblastic leukemia-mediated destruction

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer. Current therapeutic regimens have improved 5-year event-free survival rates to 90%, however clinical outcomes for high-risk subgroups, such as BCR-ABL1+ B-ALL and relapsed ALL, remain poor. In addition, 16% of newly diagnosed children with ALL present with vertebral compression fractures. Moreover, 16% of children with ALL undergoing glucocorticoid therapy also experience a high incidence of vertebral fractures, indicating that bone health may be compromised by both leukemia progression and osteotoxicity of chemotherapy.

Myeloablative Busulfan, Fludarabine and Melphalan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Childhood Myeloid Malignancy

Allogeneic hematopoietic stem cell transplant (HSCT) is a proven curative therapy for children with high-risk myeloid malignancies. Disease relapse, transplant-related mortality and graft versus host disease (GvHD) are the main causes of treatment failure and death post-transplant. The optimum pretransplant conditioning regimen is yet to be defined. There is limited data regarding the use of busulfan, fludarabine and melphalan as a myeloablative conditioning regimen in children receiving HSCT for myeloid malignancies.

Clinical and germline risk factors for multiple treatment related toxicities in pediatric acute lymphoblastic leukemia

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

Ion channel modulator DPI-201-106 significantly enhances antitumor activity of DNA damage response inhibitors in glioblastoma

Glioblastoma, a lethal high-grade glioma, has not seen improvements in clinical outcomes in nearly 30 years. Ion channels are increasingly associated with tumorigenesis, and there are hundreds of brain-penetrant drugs that inhibit ion channels, representing an untapped therapeutic resource. The aim of this exploratory drug study was to screen an ion channel drug library against patient-derived glioblastoma cells to identify new treatments for brain cancer. 

Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia: a multicentre retrospective Australian cohort study

Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML.

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.

Renal Masses in Childhood: An Australian Perspective

Childhood renal masses comprise a heterogeneous group of conditions that have a wide range of presentations. This review outlines an approach to the diagnostic work-up of childhood renal masses and discusses the most common presentations and treatments. Renal tumours make up 5% of childhood cancer in Australia, with Wilms tumour being the most common under age 10 years.

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.