Astrocytoma

P2, N=60, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Based on our index case and the 35 cases found in the literature, we suggest the archetypical histological and molecular features of "CNS tumor with BCOR/BCOR(L1)-fusion". We also present four adult diffuse glioma cases including GBM, IDH-Wildtype and Astrocytoma, IDH-Mutant with CREBBP fusions and describe the necessity of complementary molecular analysis in "CNS tumor with BCOR/BCOR(L1)-alterations for securing a final diagnosis.

P1/2, N=20, Recruiting, University of Miami | Initiation date: May 2024 --> Aug 2024

The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.

P2, N=160, Active, not recruiting, BioMimetix JV, LLC | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Aug 2023

The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

The median overall survival times were 42.86, 66.07, and 41.14 weeks for amplified, highly polysomic, and nonamplified, respectively, and were not significantly different (p =  0.3410). High chromosome 7 polysomic gliomas are rare but our data suggest that they may be biologically similar to nonamplified gliomas.

P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2028 --> May 2028

P=N/A, N=450, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2029 --> May 2029

No abstract available

EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

P1, N=8, Completed, Istari Oncology, Inc. | Active, not recruiting --> Completed | Phase classification: P1b --> P1 | N=12 --> 8

Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.

P1, N=32, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Mar 2024 --> Sep 2024

P1/2, N=58, Recruiting, Queensland Institute of Medical Research | Not yet recruiting --> Recruiting | Trial primary completion date: Aug 2026 --> Apr 2026

P2, N=37, Suspended, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.

P1, N=27, Not yet recruiting, National Cancer Institute (NCI)

Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion.

Corpus callosum involvement and extent of surgery are independent predictors of tumour dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumour enlargement at F10 and tumour migration 1-month post-RT were associated with poorer OS.

Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.

This review provides a comprehensive summary of PGK1's expression pattern, structural features, functional properties, involvement in PTMs, and interaction with tumors. Additionally highlighted are the prospects for developing and applying related inhibitors that confirm the indispensable value of PGK1 in tumor progression.

KCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.

The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.

Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors.

PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.

Additionally, the type 2 positive allosteric modulator (PAM2) PNU120596 and hydroxyurea (HU) also inhibited the binding. Our studies demonstrate that activation of α7 AChRs has efficacy in inhibiting the SARS-Cov-2 interaction with the ACE2 receptor and in such a way can prevent virus target cell penetration. These studies also help to clarify the consistent efficacy and positive outcomes for utilizing HU in treating COVID-19.

P1, N=15, Not yet recruiting, Nationwide Children's Hospital

P2, N=15, Terminated, University of Oklahoma | N=45 --> 15 | Trial completion date: Nov 2024 --> Feb 2024 | Active, not recruiting --> Terminated; Funder terminated funding.

P3, N=300, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P2, N=148, Active, not recruiting, NRG Oncology | Recruiting --> Active, not recruiting

P1, N=68, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Mar 2025 --> May 2024

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.

In summary, this is an excellent example of tumor heterogeneity both histologically and by molecular analysis. It is probable, given the clinical history of presentation 2 years prior, that this tumor originated as a low-grade glioma and subsequently evolved.

We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM.

The identified metalloproteases may play a key role in the process of gliomagenesis and may represent potential targets for personalized therapy. However, as we have not confirmed the relationship between mRNA expression and protein levels in individual samples, it is therefore natural that the regulation of metalloproteases will be subject to several factors.

Finally, analysis of multiple CCL chemokines in the macrophage secretome revealed that CXCR4 inactivation and CXCR7 activation selectively enhanced P2Y11/IL-1R-mediated secretion of CCL20. Altogether, our data establish CXCR7 as an integral component of the P2Y11/IL-1R-initiated signaling cascade and CXCR4-associated PDE4 as a regulatory checkpoint.

Oligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.

P1, N=24, Active, not recruiting, Gregory K. Friedman, MD | Recruiting --> Active, not recruiting | N=15 --> 24

P1, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Aug 2025 | Trial primary completion date: Dec 2023 --> Aug 2025