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Patient-Derived Orthotopic Xenograft Models for High-Grade Pediatric Brain Cancers

Patient-derived orthotopic xenograft (PDOX) mouse models are considered the gold standard for evidence-based preclinical research in pediatric neuro-oncology. This protocol describes the generation of PDOX models by intracranial implantation of human pediatric brain cancer cells into immune-deficient mice, and their continued propagation to establish cohorts of animals for preclinical research.

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment.

Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations

Antibodies 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.

Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action

Chemotherapy has historically been the mainstay of cancer treatment, but our understanding of what drives a successful therapeutic response remains limited.

A novel skin cancer prevention strategy: Preservice teachers' perceptions of a sun safety intervention and experiences in schools

Teachers play a vital role in developing children's sun protection routines however upskilling preservice teachers (PSTs) while at university has not yet been trialled as a targeted skin cancer prevention strategy. Hence, this study investigated PSTs perceptions and experiences of sun safety following a brief pilot intervention and placement in primary schools in Western Australia.

ErbB4 in the brain: Focus on high grade glioma

The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases (RTKs) consists of EGFR, ErbB2, ErbB3, and ErbB4. These receptors play key roles in cell proliferation, angiogenesis, cell migration, and in some cases, tumor promotion.

EphA3-targeted chimeric antigen receptor T cells are effective in glioma and generate curative memory T cell responses

High-grade gliomas including glioblastoma (GBM) and diffuse midline gliomas (DMG) represent the most lethal and aggressive brain cancers where current treatment modalities offer limited efficacy. Chimeric antigen receptor (CAR) T cell therapies have emerged as a promising strategy, boasting tumor-specific targeting and the unique ability to penetrate the blood-brain barrier.

Efficacy of DYRK1A inhibitors in novel models of Down syndrome acute lymphoblastic leukemia

Despite significant advances, outcomes for children with Down syndrome (DS, trisomy 21) who develop acute lymphoblastic leukemia remain poor. Reports of large DS-ALL cohorts have shown that children with DS have inferior event-free survival and overall survival compared to children without DS.

Characteristics of patients ≥10 years of age with diffuse intrinsic pontine glioma: a report from the International DIPG/DMG Registry

Diffuse intrinsic pontine gliomas generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry.

Acute Lymphoblastic Leukemia in Infants: A Distinctive, High-Risk Subtype of Childhood Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) in infants younger than 1 year of age is an aggressive, high-risk subtype of childhood ALL. Infant ALL with KMT2A-r is characteristically poorly responsive to chemotherapy and hematopoietic stem cell transplantation. New strategies, such as molecularly targeted therapies and immunotherapies, are in development and show promise in preclinical models and early phase studies.