temozolomide

P2, N=60, Not yet recruiting, Massachusetts General Hospital | N=40 --> 60

P1, N=68, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2027 --> Feb 2028 | Trial primary completion date: Oct 2024 --> Feb 2025

Rapid central pathology review and molecular testing for eligibility was feasible. The protocol therapy including radiation, veliparib and temozolomide was well tolerated but failed to improve outcome compared to clinically and molecularly matched historical control cohorts treated with higher doses of alkylator chemotherapy.

Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

Here, we show that the IRDS signature, linked to chemo-resistance in other cancers, can be induced in glioblastoma by microglia. ISG genes and the microglia inducing the ISG expression could be promising novel therapeutic targets in glioblastoma.

P1, N=21, Active, not recruiting, University of Florida | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P3, N=200, Not yet recruiting, Vastra Gotaland Region | Initiation date: May 2024 --> Dec 2024

ALDH1A1 is a primary metabolic enzyme impacting the outcome of chemotherapy, including temozolomide...Evidence from a nationwide cancer registry has suggested PPIs have a negative impact on OS for GBM patients, particularly those with MGMT promoter methylation. This suggests PPIs should be avoided for prophylactic management of gastrointestinal toxicity in patients with GBM receiving chemoradiotherapy.

They have been evaluated both alone and in combination with radiotherapy, temozolomide, anti-angiogenic agents, immunotherapy and other new drugs in newly diagnosed or recurrent glioma...In conclusion, early phase studies have shown promising anti-tumour activity of PARPi that should be confirmed in larger prospective and randomised trials. In addition, the development of novel PARPi with improved blood brain barrier (BBB) penetration and PARP inhibitor activity with new synergistic treatment combinations seems promising and needs to be further explored.

Trimodal therapy comprising surgical resection, pRT and TMZ-based chemotherapy appears to have the most beneficial effect on survival in GSM patients. Smaller tumor size, younger age and methylated MGMT promoters are associated with improved survival. To our knowledge, this is the largest multi-institutional cohort study investigating outcomes and prognostic factors for GSM.

ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Furthermore, mechanistic exploration revealed that T+A@Glu-NPs degraded the BRD4 protein, leading to the downregulation of Notch1 gene transcription and the inhibition of the Notch1 signaling pathway, thereby augmenting the therapeutic efficacy of glioma chemotherapy. Taken together, the findings suggest that T+A@Glu-NPs represents a novel and promising therapeutic strategy for glioma chemotherapy.

The findings suggest that symptomatic glioma enhances inflammatory responses linked to poor prognosis and chemoresistance. This supports the hypothesis that immediate treatment of incidental glioma may improve patient outcomes over a wait-and-see approach.

Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.

P2, N=40, Not yet recruiting, Massachusetts General Hospital | N=60 --> 40

Here we investigated the effect of glutamine deprivation on cellular metabolism and sensitivity of human glioblastoma cells U87MG and T98G to drugs of various origin: alkylating cytostatic agent temozolomide; cytokine TRAIL DR5-B - agonist of the DR5 receptor; and GMX1778 - a targeted inhibitor of the enzyme nicotinamide phosphoribosyltransferase (NAMPT), limiting NAD biosynthesis. Thus, phenotypic and metabolic differences between the two human glioblastoma cell lines caused divergent metabolic changes and contrasting responses to different targeted drugs during glutamine deprivation. These data should be considered when developing treatment strategies for glioblastoma via drug-mediated deprivation of amino acids, as well as when exploring novel therapeutic targets.

Applying this method to adult and childhood brain cancers, we identify critical regulators and suggest interventions that could improve temozolomide treatment in glioblastoma...Finally, scregclust's flexibility is demonstrated across 15 tumor types, uncovering both pan-cancer and specific regulators. The algorithm is provided as an easy-to-use R package that facilitates the exploration of regulatory programs underlying cell plasticity.

Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem.

In this study, a comprehensive analysis of the expression of 361 DNA repair genes and activation levels of 38 DNA repair pathways revealed 13 potential survival biomarkers with increased prognostic potential compared to MGMT methylation. We algorithmically reconstructed the TMZ sensitivity pathway with strong predictive capacity in GBM.

Co-inhibition of AUF1 expression with miR-505-5p/-3p knockdown ameliorated the observed cellular phenotypes caused by miR-505-5p/-3p knockdown in MES-GSCs. These results suggest that miR-505-5p/-3p exerts MES-GSC-specific roles in regulating proliferation, differentiation, invasion, apoptosis, and temozolomide resistance by repressing AUF1 expression.

Our study reveals a novel regulatory mechanism in which the Cx43/miR-205-5p/E2F1/ERCC1 axis contributes to TMZ resistance in glioma. These findings further highlight the potential of targeting Cx43 as a therapeutic strategy in glioma.

P1, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality. Our findings show that besides HSPC, also MSC are sensitive to certain antineoplastic agents, resulting in molecular and functional alterations that may contribute to therapy-related myelosuppression. Understanding these interactions could be helpful for the development of strategies to preserve BM MSC functionality during different kinds of anticancer therapies.

P=N/A, N=982, Active, not recruiting, NovoCure Ltd. | Trial completion date: Aug 2026 --> Jan 2026 | Trial primary completion date: Aug 2024 --> Jan 2026

P3, N=32, Recruiting, NaviFUS Corporation | Not yet recruiting --> Recruiting

P2, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

P2, N=83, Active, not recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=18, Active, not recruiting, Cantex Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=60, Not yet recruiting, Rigel Pharmaceuticals | Initiation date: Jun 2024 --> Nov 2024

P2, N=40, Not yet recruiting, Affiliated Cancer Hospital of Shandong First Medical University; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandon

P2, N=57, Active, not recruiting, Oblato, Inc. | Trial completion date: Jan 2025 --> May 2025

P2, N=152, Not yet recruiting, VA Office of Research and Development

P2, N=62, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Not yet recruiting --> Recruiting

P2, N=28, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

HT is promising for glioblastomas (GBM), especially complex cases with infratentorial involvement or multiple lesions. This study highlighted the potential clinical significance of systemic inflammation indicators in predicting survival and disease progression.

P2, N=55, Active, not recruiting, Dwight Owen | Trial primary completion date: Jul 2024 --> Dec 2024

The obtained qRT-PCR and proteomics data highlight the modulation of cell death via apoptosis (BAX/BCL2, CASP9) and autophagy (BECN1, BNIP3, BNIP3L and LC3B), as well as an epithelial to mesenchymal transition blockage (HTRA1, SERPINE1, WNT5A, ALDH3B1 and EPHA2) and remodeling of the extracellular matrix (VCAN, SERPINE1 and TGFBI). Overall, these results lay the foundation for further investigations on the potential combinatory clinical treatment with temozolomide.

p21CIP1 is essentially involved in induction and maintenance of irinotecan-induced senescence. Neither p16INK4A, p14ARF, nor PTEN contribute to senescence, if p21CIP1 cannot be induced. Based on the positive results of the irinotecan/BV6 treatment, combatting recurrent glioblastomas by targeting senescence cell antiapoptotic pathways (SCAPs) should be considered.

HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

P4, N=11, Suspended, Children's Hospital Los Angeles | Trial completion date: Aug 2024 --> Jun 2025 | Recruiting --> Suspended | Trial primary completion date: Aug 2024 --> Jun 2025

P3, N=40, Recruiting, N.N. Petrov National Medical Research Center of Oncology

P1/2, N=18, Active, not recruiting, University of Louisville | Recruiting --> Active, not recruiting | N=40 --> 18