DNX-2401: an investigational drug for the treatment of recurrent glioblastoma.

DNX-2401: an investigational drug for the treatment of recurrent glioblastoma. Expert Opin Investig Drugs. 2019 Nov 14;: Authors: Philbrick B, Adamson DC Abstract INTRODUCTION: High grade gliomas (HGG) are extremely aggressive brain malignancies that are usually fatal. Despite maximal resection, chemotherapy and radiation, these tumors inevitably recur and present a poor median overall survival (mOS); hence there is a pressing need for improved treatments.Areas covered:This review assesses DNX-2401 as a treatment of recurrent HGG. Phase I data on efficacy, safety, and tolerability are examined while insights and perspectives on future directions are offered.Expert opinion:This phase I study assessed DNX-2401 in two groups; one group received a one-time intratumoral injection of DNX-2401 without tumor resection while the second group received an intratumoral injection of DNX-2401 followed by surgical resection 14 days later and a second injection of DNX-2401 into the resection cavity. In patients that did not receive resection, the mOS was 9.5 months across all cohorts while patients in the resection group had a mOS of 13 months which is a promising extension of survival compared to historical controls. Furthermore, this study had numerous long-term survivors living for greater than 2 years at the time of recurrence. DNX-2401 was well tolerated with no drug-related Grade 3 or greater adverse events; it demonstrated some ability to provoke an immunologic re...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

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AbstractExisting drug delivery methods have not led to a significant increase in survival for patients with malignant primary brain tumors. While the combination of conventional therapies consisting of surgery, radiotherapy, and chemotherapy has improved survival for some types of brain tumors (e.g., WNT medulloblastoma), other types of brain tumors (e.g., glioblastoma and diffuse midline glioma) still have a poor prognosis. The reason for the differences in response can be largely attributed to the blood –brain barrier (BBB), a specialized structure at the microvasculature level that regulates the transport of molec...
Source: CNS Drugs - Category: Neurology Source Type: research
In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
We describe a case of recurrent glioblastoma treated with anlotinib in this report. The patient was administered anlotinib 12 mg p.o. every day (days 1-14, with a 21-day cycle) (anlotinib clinical study NCT04004975) and oral temozolomide chemotherapy 100 mg/m2 (days 1-7, days 15-21, 28-day cycle; 12 cycles). After 2 months of therapy, the patient achieved a partial response that has been maintained for>17 months of follow-up. Molecular characterization confirmed the presence of a TERT promoter mutation, wild-type IDH1/2, an FGFR3-TACC3 fusion, and FGFR3 amplification in the patient. Anlotinib is a multitarget tyrosine k...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
This study has thus identified a simple transcriptome signature for GBM prognosis. PMID: 32931454 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Abstract Glioblastoma Multiforme (GBM) is an aggressive brain tumor (WHO grade 4 astrocytoma) with unknown causes and is associated with a reduced life expectancy. The available treatment options namely radiotherapy, surgery and chemotherapy have failed to improve life expectancy. Out of the various therapeutic approaches, epigenetic therapy is one of the most studied. Epigenetic therapy is involved in the effective treatment of GBM by inhibiting DNA methyltransferase, histone deacetylation and non-coding RNA. It also promotes the expression of the tumor suppressor gene and is involved in the suppression of the on...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
In conclusion, the silencing of TXNDC9 induces apoptosis and autophagy in glioma and promotes cell differentiation by controlling p53 and may function as a new mechanism in glioma. PMID: 32897242 [PubMed - as supplied by publisher]
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Abstract OBJECTIVE: Anaplastic gliomas (AGs) are an extremely heterogeneous group of primary brain tumors. More recently, new discoveries have indicated that isocitrate dehydrogenase (IDH) mutation status is the most important parameter predicting survival. The primary aim of the present analysis was to identify prognostic factors, other than IDH status, that eventually impact survival. METHODS: Patients with available clinical, imaging, and molecular profile data who were amenable to resection were evaluated. The extent of resection (EOR) was defined as gross-total resection (GTR), near-total resection (NTR)...
Source: Journal of Neurosurgery - Category: Neurosurgery Authors: Tags: J Neurosurg Source Type: research
Abstract Glioma is the most common type of brain cancer. Chemotherapy combination with surgery and radiotherapy is a standard treatment for patients. Although there are many advances in glioma therapy, the prognosis of glioma patients has not significantly been improved over the past decades. Hence, there is still an urgent need to develop a new therapy to treat glioma. Cell viability was assessed by CellTiter Blue assay; flow cytometry (FCM) was used for detecting cell apoptosis; ROS detection was detected by ROS Assay; H2O2 detection was performed by hydrogen peroxide detection kits; real-time PCR and WB were us...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
(NRG Oncology) A practice-changing study, NRG Oncology clinical trial NRG-RTOG 9802, has demonstrated, for the first time, a survival benefit of adjuvant chemotherapy following radiotherapy over radiotherapy alone in certain subgroups of patients with high-risk, low-grade glioma (WHO classification: LGG, grade II), a type of brain tumor that originates from glial cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Conclusion: The present study suggests that the currently used arc-based radiotherapy and chemotherapy might affect cognitive function less negatively than previously described during treatment and in the first year after treatment in malignant glioma patients. In general, a high cognitive test score at baseline was associated with longer time to progression and with longer survival. PMID: 32847475 [PubMed - in process]
Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
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