A scoping review of diffuse hemispheric glioma, H3 G34-mutant: Epigenetic and molecular profiles, clinicopathology, and treatment avenues.

Background: Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for diffuse hemispheric glioma (DHG), H3 G34-mutant, which is often present in adolescent and young adult patients. This scoping review consolidates existing knowledge of DHG H3 G34-mutant and identifies future targets and therapeutic options.

Central nervous system tumors in adolescents and young adults: A Society for Neuro-Oncology consensus review on diagnosis, management, and future directions.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

Enhancing neuro-oncology care through equity-driven applications of artificial intelligence.

The disease course and clinical outcome for brain tumor patients depend not only on the molecular and histological features of the tumor but also on the patient's demographics and social determinants of health. While current investigations in neuro-oncology have broadly utilized artificial intelligence (AI) to enrich tumor diagnosis and more accurately predict treatment response, postoperative complications, and survival, equity-driven applications of AI have been limited. However, AI applications to advance health equity in the broader medical field have the potential to serve as practical blueprints to address known disparities in neuro-oncologic care.

Social Determinants of Health in Cardio-Oncology: Multi-Level Strategies to Overcome Disparities in Care: State-of-the-Art Review.

Addressing the need for more equitable cardio-oncology care requires attention to existing disparities in cardio-oncologic disease prevention and outcomes. This is particularly important among those affected by adverse social determinants of health (SDOH). The intricate relationship of SDOH, cancer diagnosis, and outcomes from cardiotoxicities associated with oncologic therapies is influenced by sociopolitical, economic, and cultural factors.

Defining interventions and metrics to improve diversity in CNS clinical trial participation: A SNO and RANO effort.

Despite major strides in cancer research and therapy, these advances have not been equitable across race and ethnicity. Historically marginalized groups (HMG) are more likely to have inadequate preventive screening, increased delays in diagnosis, and poor representation in clinical trials. Notably, Black, Hispanic, and Indigenous people represent 30% of the population but only 9% of oncology clinical trial participants.

Clinical protocol: Feasibility of evaluating abemaciclib neuropharmacokinetics of diffuse midline glioma using intratumoral microdialysis.

Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity.

The NIH pediatric/young adult chordoma clinic and natural history study: Making advances in a very rare tumor.

Background: Chordomas are rare tumors arising from the skull base and spine, with approximately 20 pediatric chordoma cases in the Unitedn States per year. The natural history and optimal treatment of pediatric chordomas, especially poorly differentiated and dedifferentiated subtypes, is incompletely understood. Herein, we present findings from our first National Cancer Institute (NCI) chordoma clinic and a retrospective analysis of published cases of pediatric poorly differentiated chordomas (PDC) and dedifferentiated chordomas (DC).

A scoping review of pediatric microdialysis: A missed opportunity for microdialysis in the pediatric neuro-oncology setting.

Background: Brain microdialysis is a minimally invasive technique for monitoring analytes, metabolites, drugs, neurotransmitters, and/or cytokines. Studies to date have centered on adults with traumatic brain injury, with a limited number of pediatric studies performed. This scoping review details past use of brain microdialysis in children and identifies potential use for future neuro-oncology trials.

New Developments in the Pathogenesis, Therapeutic Targeting, and Treatment of H3K27M-Mutant Diffuse Midline Glioma.

H3K27M-mutant diffuse midline gliomas (DMGs) are rare childhood central nervous system tumors that carry a dismal prognosis. Thus, innovative treatment approaches are greatly needed to improve clinical outcomes for these patients. Here, we discuss current trends in research of H3K27M-mutant diffuse midline glioma.

Adenosine A2A Receptor Activation Enhances Blood-Tumor Barrier Permeability in a Rodent Glioma Model.

The blood-tumor barrier (BTB) limits the entry of effective chemotherapeutic agents into the brain for treatment of malignant tumors like glioblastoma. Poor drug entry across the BTB allows infiltrative glioma stem cells to evade therapy and develop treatment resistance. Regadenoson, an FDA-approved adenosine A2A receptor (A2AR) agonist, has been shown to increase drug delivery across the blood-brain barrier in non-tumor-bearing rodents without a defined mechanism of enhancing BTB permeability.

Affirming NIH's commitment to addressing structural racism in the biomedical research enterprise.

NIH has acknowledged and committed to ending structural racism. The framework for NIH's approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.

Inhibiting protein phosphatase 2A increases the antitumor effect of protein arginine methyltransferase 5 inhibition in models of glioblastoma.

Background: Despite multi-model therapy of maximal surgical resection, radiation, chemotherapy, and tumor-treating fields, the median survival of glioblastoma (GBM) patients is less than 15 months. Protein arginine methyltransferase 5 (PRMT5) catalyzes the symmetric dimethylation of arginine residues and is overexpressed in GBM. Inhibition of PRMT5 causes senescence in stem-like GBM tumor cells.

The MEK inhibitor selumetinib reduces spinal neurofibroma burden in patients with NF1 and plexiform neurofibromas.

Background: Spinal neurofibromas (SNFs) in neurofibromatosis type 1 (NF1) can cause progressive spinal cord compression and neurological dysfunction. The MEK inhibitor selumetinib shrinks the majority of plexiform neurofibromas (PNs) in patients with NF1. We assessed the effect of selumetinib on SNF.

Model systems for studying the blood-brain barrier: Applications and challenges.

The blood-brain barrier (BBB) poses a serious impediment to the delivery of effective therapies to the central nervous system (CNS). Over time, various model systems have been crafted and used to evaluate the complexities of the BBB, which includes an impermeable physical barrier and a series of energy-dependent efflux pumps. Models of the BBB have mainly sought to assess changes in endothelial cell permeability, the role of ATP-dependent efflux transporters in drug disposition, and alterations in communication between BBB cells and the microenvironment.

Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade.

Background: Glioblastoma is the most common primary malignancy of the brain, with a dismal prognosis. Immunomodulation via checkpoint inhibition has provided encouraging results in non-CNS malignancies, but prediction of responders has proven to be challenging in glioblastoma patients.

Objective: To determine the proportion of patients who have a measurable increase of interferon gamma levels in brain tumor tissue after their first dose of nivolumab, and to evaluate the safety of using brain tumor microdialysis to monitor for immune response while evaluating the safety of the combination of anti-programmed death 1 (PD-1) and anti-lymphocyte activation gene 3 (LAG-3) checkpoint inhibition.

The effect of an adenosine A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma.

Background: The blood-brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma.

Targeting WNT Signaling for Multifaceted Glioblastoma Therapy.

The WNT signaling pathway has been of great interest to developmental biologists for decades and has more recently become a central topic for study in cancer biology. It is vital for cell growth and regulation of embryogenesis in many organ systems, particularly the CNS and its associated vasculature. We summarize the role of WNT in CNS development and describe how WNT signaling makes key contributions to malignant glioma stemness, invasiveness, therapeutic resistance, and angiogenesis.

Blood-brain barrier pericyte importance in malignant gliomas: what we can learn from stroke and Alzheimer's disease.

The pericyte, a constitutive component of the central nervous system, is a poorly understood cell type that envelops the endothelial cell with the intended purpose of regulating vascular flow and endothelial cell permeability. Previous studies of pericyte function have been limited to a small number of disease processes such as ischemic stroke and Alzheimer's disease. Recently, publications have postulated a link between glioma stem cell differentiation and pericyte function.