scholarly journals ONCOLYTIC VIRUSES IN HIGH-GRADE GLIOMAS TREATMENT

2015 ◽  
Vol 6 (2) ◽  
pp. 46-59 ◽  
Author(s):  
V P Baklaushev ◽  
S A Goryainov ◽  
А А Potapov ◽  
G V Pavlova ◽  
V P Chehonin
Keyword(s):  
Clinical Trials ◽  
Clinical Guidelines ◽  
Laboratory Tests ◽  
State Of The Art ◽  
Malignant Gliomas ◽  
Point Of View ◽  
Oncolytic Viruses ◽  
High Grade ◽  
Preclinical Trials ◽  
High Grade Gliomas

The review examines the state of the art of diagnosis and therapy of high-grade gliomas both by currently existing clinical guidelines, and from the point of view of the most promising approaches of currently undergoing laboratory tests and the first clinical trials. One of the most promising approach for the treatment of malignant gliomas is the nonpathogenic oncolytic viruses (OV) application. The data of preclinical trials of OV and the first preliminary results of clinical trials are discussed.

scholarly journals Against the Resilience of High-Grade Gliomas: Gene Therapies (Part II)

2021 ◽  
Vol 11 (8) ◽  
pp. 976
Author(s):  
Alice Giotta Lucifero ◽  
Sabino Luzzi
Keyword(s):  
Clinical Trials ◽  
Tumor Suppressor ◽  
Literature Review ◽  
Target Genes ◽  
Suicide Gene ◽  
Oncolytic Viruses ◽  
High Grade ◽  
Gene Target ◽  
Gene Therapies ◽  
High Grade Gliomas

Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies.

scholarly journals Viral therapies for glioblastoma and high-grade gliomas in adults: a systematic review

2021 ◽  
Vol 50 (2) ◽  
pp. E2
Author(s):  
Joshua L. Wang ◽  
Kristen M. Scheitler ◽  
Nicole M. Wenger ◽  
J. Bradley Elder
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Viral Vectors ◽  
Cytosine Deaminase ◽  
Treatment Strategies ◽  
Oncolytic Viruses ◽  
Phase Iii ◽  
Viral Gene ◽  
High Grade ◽  
High Grade Gliomas

OBJECTIVEHigh-grade gliomas (HGGs) inevitably recur and progress despite resection and standard chemotherapies and radiation. Viral therapies have emerged as a theoretically favorable adjuvant modality that might overcome intrinsic factors of HGGs that confer treatment resistance.METHODSThe authors present the results of systematic searches of the MEDLINE and ClinicalTrials.gov databases that were performed for clinical trials published or registered up to July 15, 2020.RESULTSFifty-one completed clinical trials were identified that made use of a virus-based therapeutic strategy to treat HGG. The two main types of viral therapies were oncolytic viruses and viral vectors for gene therapy. Among clinical trials that met inclusion criteria, 20 related to oncolytic viruses and 31 to gene therapy trials. No oncolytic viruses have progressed to phase III clinical trial testing, although there have been many promising early-phase results and no reported cases of encephalitis or death due to viral therapy. Three phase III trials in which viral gene therapy was used have been completed but have not resulted in any FDA-approved therapy. Recent efforts in this area have been focused on the delivery of suicide genes such as herpes simplex virus thymidine kinase and cytosine deaminase.CONCLUSIONSDecades of research efforts and an improving understanding of the immunomodulatory effects of viral therapies for gliomas are informing ongoing clinical efforts aimed at improving outcomes in patients with HGG. The available clinical data reveal varied efficacy among different virus-based treatment strategies.

scholarly journals Management of high-grade gliomas in the pediatric patient: Past, present, and future

2014 ◽  
Vol 1 (4) ◽  
pp. 145-157 ◽  
Author(s):  
Magimairajan Issai Vanan ◽  
David D. Eisenstat
Keyword(s):  
Clinical Trials ◽  
Malignant Gliomas ◽  
Treatment Strategies ◽  
Multimodality Treatment ◽  
Driver Mutations ◽  
Histopathological Diagnosis ◽  
High Grade ◽  
Minimal Impact ◽  
Resected Tumor ◽  
High Grade Gliomas

Abstract High-grade gliomas (HGGs) constitute ∼15% of all primary brain tumors in children and adolescents. Routine histopathological diagnosis is based on tissue obtained from biopsy or, preferably, from the resected tumor itself. The majority of pediatric HGGs are clinically and biologically distinct from histologically similar adult malignant gliomas; these differences may explain the disparate responses to therapy and clinical outcomes when comparing children and adults with HGG. The recently proposed integrated genomic classification identifies 6 distinct biological subgroups of glioblastoma (GBM) throughout the age spectrum. Driver mutations in genes affecting histone H3.3 (K27M and G34R/V) coupled with mutations involving specific proteins (TP53, ATRX, DAXX, SETD2, ACVR1, FGFR1, NTRK) induce defects in chromatin remodeling and may play a central role in the genesis of many pediatric HGGs. Current clinical practice in pediatric HGGs includes surgical resection followed by radiation therapy (in children aged > 3 years) with concurrent and adjuvant chemotherapy with temozolomide. However, these multimodality treatment strategies have had a minimal impact on improving survival. Ongoing clinical trials are investigating new molecular targets, chemoradiation sensitization strategies, and immunotherapy. Future clinical trials of pediatric HGG will incorporate the distinction between GBM molecular subgroups and stratify patients using group-specific biomarkers.

scholarly journals Sonodynamic Therapy for the Treatment of Intracranial Gliomas

2021 ◽  
Vol 10 (5) ◽  
pp. 1101
Author(s):  
Antonio D’Ammando ◽  
Luca Raspagliesi ◽  
Matteo Gionso ◽  
Andrea Franzini ◽  
Edoardo Porto ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
High Grade ◽  
Sonodynamic Therapy ◽  
Treatment Protocols ◽  
Ultrasound Waves ◽  
High Grade Gliomas ◽  
Preclinical And Clinical Studies

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

Phase II Trial of Thalidomide and Carmustine for Patients With Recurrent High-Grade Gliomas

2003 ◽  
Vol 21 (12) ◽  
pp. 2299-2304 ◽  
Author(s):  
Howard A. Fine ◽  
Patrick Y. Wen ◽  
Elizabeth A. Maher ◽  
Elene Viscosi ◽  
Tracy Batchelor ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Malignant Gliomas ◽  
Cytotoxic Agents ◽  
Clinical Activity ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Antiangiogenic Agent ◽  
Histologic Diagnosis ◽  
Anaplastic Gliomas ◽  
High Grade Gliomas

Purpose: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. Patients and Methods: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. Results: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. Conclusion: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.

scholarly journals ONCOLYTIC VIROTHERAPY IN GLIOBLASTOMA TREATMENT: PROGRESS AND CHALLENGES IN CLINICAL RESEARCH (LITERATURE REVIEW)

2020 ◽  
Vol 19 (6) ◽  
pp. 133-140
Author(s):  
O. I. Kit ◽  
S. N. Ignatov ◽  
E. Yu. Zlatnik ◽  
N. V. Soldatkina ◽  
E. E. Rostorguev ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Viral Vectors ◽  
Experimental Studies ◽  
Research Literature ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
High Grade ◽  
Treatment Progress ◽  
Poor Treatment ◽  
Target Cancer

Glial tumors comprise about 60 % of primary malignant brain tumors, and 70 % of them show morphological signs of high-grade cancer (High Grade Gliomas III , IV WHO 2016) [1, 2]. Despite a significant technical pre- and intraoperative progress as well as advances in radiotherapy and chemotherapy, the overall median survival is very low, being less than 20 months [3] and less than 12 months in patients with relapse [4]. Recent studies have shown that chemo- and radioresistance is due to the existence of cancer stem cells [5, 6]. Poor treatment outcomes require the development and implementation of new approaches to the treatment of highgrade gliomas. In recent years, increasing attention has been paid to the development of immunotherapeutic treatment approaches, including the development of oncolytic virotherapy. Tropism to target cancer cells, as well as various viral vectors, has been developed using methods of genetic engineering; synergism of viruses and adjuvant therapy has been studied. Despite extensive experimental studies of the mechanism of oncolysis [1], there are only a few reports on Phase I–II clinical trials. This review considers the most successful applications of oncolytic viruses in relation to glioblastoma in animal models and their translation into clinical practice in patients.

Current strategies for the treatment of malignant gliomas – experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw

2020 ◽  
Vol 92 (4) ◽  
pp. 1-5
Author(s):  
Grzegorz Turek ◽  
Tomasz Pasterski ◽  
Krzysztof Bankiewicz ◽  
Sebastian Dzierzęcki ◽  
Mirosław Ząbek
Keyword(s):  
Brain Tumors ◽  
San Francisco ◽  
Malignant Gliomas ◽  
High Grade ◽  
Current Standard ◽  
Convection Enhanced Delivery ◽  
Surgical Methods ◽  
High Grade Gliomas ◽  
Standard Medical Treatment ◽  
Intraoperative Electrical Stimulation

Introduction: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. Material and methods: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management – from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. Results: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. Discussion: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

scholarly journals Outcome of high-grade gliomas (HGGs) treated into immunotherapeutic early-phase clinical trials (ieCTs): A single-center experience

2019 ◽  
Vol 30 ◽  
pp. v155-v156
Author(s):  
M. Simonelli ◽  
P. Persico ◽  
A. Dipasquale ◽  
E. Lorenzi ◽  
L. Giordano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
High Grade ◽  
Single Center ◽  
Single Center Experience ◽  
High Grade Gliomas ◽  
Early Phase Clinical Trials

scholarly journals Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives

2021 ◽  
Vol 10 (7) ◽  
pp. 1367
Author(s):  
Pasquale Persico ◽  
Elena Lorenzi ◽  
Angelo Dipasquale ◽  
Federico Pessina ◽  
Pierina Navarria ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
State Of The Art ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Immune Checkpoint Blockade ◽  
High Grade ◽  
Current Standard ◽  
Advanced Malignancies ◽  
The Status ◽  
High Grade Gliomas

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in many advanced malignancies. Unfortunately, these clinical successes have not been replicated in the neuro-oncology field so far. This review summarizes the status of ICI investigation in high-grade gliomas, critically presenting the available data from preclinical models and clinical trials. Moreover, we explore new approaches to increase ICI efficacy, with a particular focus on combinatorial strategies, and the potential biomarkers to identify patients most likely to benefit from immune checkpoint blockade.

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