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Neurosurgical Review Dec 2019The oncological impact of cytoreductive surgery for malignant glioma has been analyzed in a few prospective, randomized studies; however, the impact of different... (Review)
Review
The oncological impact of cytoreductive surgery for malignant glioma has been analyzed in a few prospective, randomized studies; however, the impact of different cytoreductive surgical techniques of cerebral tumors remains controversial. Despite retrospective analyses revealing an oncological impact of complete surgical resection in cerebral metastases and low-grade glioma, the oncological impact of further extension of resection to a supramarginal resection remains disputable lacking high-grade evidence: supramarginal resections have yet to be analyzed in malignant glioma. Although extension of resection towards a supramarginal resection was thought to improve outcome and prevent malignant transformation in low-grade glioma, the rate of (temporary) deficits was higher than 50% in recent retrospective studies, and the oncological impact and long-term results have to be analyzed in further (prospective and controlled) studies. Cerebral metastases show a growth pattern different from glioma with less and more locally limited brain invasion. Therefore, local control may be achieved by extension of resection after complete lesionectomy of cerebral metastases. Therefore, supramarginal resection may be a promising approach but must be evaluated in further studies.
Topics: Brain Neoplasms; Glioma; Humans; Neoplasm Grading; Treatment Outcome
PubMed: 29556836
DOI: 10.1007/s10143-018-0963-z -
Acta Neurologica Belgica Sep 2017Despite the numerous promising discoveries in contemporary cancer research and the emerging innovative cancer treatment strategies, the global burden of malignant glioma... (Review)
Review
Despite the numerous promising discoveries in contemporary cancer research and the emerging innovative cancer treatment strategies, the global burden of malignant glioma is expected to increase, partially due to its poor prognosis and human aging. Dopamine, a monoamine catecholamine neurotransmitter, is currently regarded as an important endogenous regulator of tumor growth. Dopamine may be an important treatment for brain tumors and could impact the pathogenesis of glioma by regulating tumor angiogenesis and vasculogenesis. Additionally, dopamine might exert an anti-glioma, cytotoxic effect by modulating apoptosis and autophagy. Dopamine and its receptors are also known to influence the immune system, as it is related to the pathogenesis of glioma. Dopamine may also increase the efficacy of anti-cancer drugs. Here, we review the potential roles of dopamine in malignant glioma and further identify the previously unknown function of dopamine as a potent regulator in the pathogenesis of glioma. Currently, the precise mechanisms regarding the protective effect of dopamine on glioma are poorly understood. However, our experimental results strongly emphasize the importance of this topic in future investigations.
Topics: Brain Neoplasms; Dopamine; Glioma; Humans
PubMed: 27995487
DOI: 10.1007/s13760-016-0730-2 -
Handbook of Clinical Neurology 2016Glioblastoma is the most common and aggressive primary brain tumor in adults. Over the past three decades, the overall survival time has only improved by a few months,... (Review)
Review
Glioblastoma is the most common and aggressive primary brain tumor in adults. Over the past three decades, the overall survival time has only improved by a few months, therefore novel alternative treatment modalities are needed to improve clinical management strategies. Such strategies should ultimately extend patient survival. At present, the extensive insight into the molecular biology of gliomas, as well as into genetic engineering techniques, has led to better decision processes when it comes to modifying the genome to accommodate suicide genes, cytokine genes, and tumor suppressor genes that may kill cancer cells, and boost the host defensive immune system against neoantigenic cytoplasmic and nuclear targets. Both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment. Stem cells, microRNAs, nanoparticles, and viruses have also been designed. These have been armed with transgenes or peptides, and have been used both in laboratory-based experiments as well as in clinical trials, with the aim of improving selective killing of malignant glioma cells while sparing normal brain tissue. This chapter reviews the current status of gene therapies for malignant gliomas and highlights the most promising viral and cell-based strategies under development.
Topics: Animals; Brain Neoplasms; Genetic Therapy; Glioma; Humans; Oncolytic Viruses
PubMed: 26948355
DOI: 10.1016/B978-0-12-802997-8.00011-6 -
Neurotherapeutics : the Journal of the... Apr 2017Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with... (Review)
Review
Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. The concept of virotherapy for the treatment of malignant tumors dates back more than a century and can be divided into replication-competent oncolytic viruses and replication-deficient viral vectors. Oncolytic viruses are designed to selectively target, infect, and replicate in tumor cells, while sparing surrounding normal brain. A host of oncolytic viruses has been evaluated in early phase human trials with promising safety results, but none has progressed to phase III trials. Despite the 25 years that has passed since the initial publication of genetically engineered oncolytic viruses for the treatment of glioma, much remains to be learned about the use of this therapy, including its mechanism of action, optimal treatment paradigm, appropriate targets, and integration with adjuvant agents. Oncolytic viral therapy for glioma remains promising and will undoubtedly impact the future of patient care.
Topics: Adenoviridae; Animals; Brain Neoplasms; Clinical Trials as Topic; Genetic Vectors; Glioma; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Paramyxoviridae; Parvovirus; Poliovirus; Reoviridae; Treatment Outcome; Virus Replication
PubMed: 28265902
DOI: 10.1007/s13311-017-0516-0 -
Neurotherapeutics : the Journal of the... Oct 2022Glioblastoma is the most common primary malignant brain tumor in adults and outcomes remain poor despite the current standard of care multimodal therapy. Oncolytic... (Review)
Review
Glioblastoma is the most common primary malignant brain tumor in adults and outcomes remain poor despite the current standard of care multimodal therapy. Oncolytic virotherapy utilizes engineered viruses to exert an anti-tumor effect via both direct oncolysis and stimulation of an immune response within the tumor microenvironment, turning tumors from "cold" to "hot." This has shown promise as a novel therapeutic modality and attempts to circumvent the challenges associated with traditional treatments. Many oncolytic viruses have been investigated in completed and ongoing clinical trials and while safety has been demonstrated, clinical outcomes have been variable, often with only a subgroup of patients showing a significant response. This review summarizes these studies, addresses relevant technical aspects of oncolytic virus administration, and highlights practical considerations to assist providers in appropriately caring for patients treated with oncolytic virotherapy. Additionally, future directions within the field that may help to maximize efficacy of this modality are discussed.
Topics: Humans; Oncolytic Virotherapy; Glioma; Oncolytic Viruses; Glioblastoma; Viruses; Tumor Microenvironment
PubMed: 35674873
DOI: 10.1007/s13311-022-01256-1 -
Expert Reviews in Molecular Medicine Mar 2023Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18... (Review)
Review
Glioblastoma (GBM) is the most frequent adult malignant brain tumour and despite different therapeutic efforts, the median overall survival still ranges from 14 to 18 months. Thus, new therapeutic strategies are urgently needed. However, the identification of cancer-specific targets is particularly challenging in GBM, due to the high heterogeneity of this tumour in terms of histopathological, molecular, genetic and epigenetic features. Telomerase reactivation is a hallmark of malignant glioma. An activating mutation of the hTERT gene, encoding for the active subunit of telomerase, is one of the molecular criteria to establish a diagnosis of GBM, IDH-wildtype, in the 2021 WHO classification of central nervous system tumours. Telomerase inhibition therefore represents, at least theoretically, a promising strategy for GBM therapy: pharmacological compounds, as well as direct gene expression modulation therapies, have been successfully employed in and settings. Unfortunately, the clinical applications of telomerase inhibition in GBM are currently scarce. The aim of the present systematic review is to provide an up-to-date report on the studies investigating telomerase inhibition as a therapeutic strategy for malignant glioma in order to foster the future translational and clinical research on this topic.
Topics: Adult; Humans; Telomerase; Glioma; Brain Neoplasms; Glioblastoma; Genetic Therapy
PubMed: 36919343
DOI: 10.1017/erm.2023.6 -
Advanced Drug Delivery Reviews Jul 2022Malignant gliomas are the most common primary brain cancer diagnosed and still carry a poor prognosis despite aggressive multimodal management. Despite the continued... (Review)
Review
Malignant gliomas are the most common primary brain cancer diagnosed and still carry a poor prognosis despite aggressive multimodal management. Despite the continued advances in immunotherapy for other cancer types, however, there remain no FDA approved immunotherapies for cancers such as glioblastoma. OF the many approaches being explored, cancer vaccine programs are undergoing a renaissance due to the technological advances and personalized nature of their contemporary design. Neoantigen vaccines are a form of immunotherapy involving the use of DNA, mRNA, and proteins derived from non-synonymous mutations identified in patient tumor tissue samples to stimulate tumor-specific T-cell reactivity leading to enhance tumor targeting. In the last several years, the study of neoantigens as a therapeutic target has increased, with the routine workflow implementation of comprehensive next generation sequencing and in silico peptide binding prediction algorithms. Several neoantigen vaccine platforms are being evaluated in clinical trials for malignancies including melanoma, pancreatic cancer, breast cancer, lung cancer, and glioblastoma, among others. In this review, we will review the concept of neoantigen discovery using cancer immunogenomics approaches in glioblastoma and explore the disease-specific issues being addressed in the design of effective personalized cancer vaccine strategies.
Topics: Antigens, Neoplasm; Cancer Vaccines; Glioblastoma; Glioma; Humans; Immunologic Factors; Immunotherapy; Neoplasms; Vaccination
PubMed: 35487282
DOI: 10.1016/j.addr.2022.114312 -
Advances in Experimental Medicine and... 2015Glioblastoma remains a tumor with a dismal prognosis because of failure of current treatment. Glioblastoma cells with stem cell (GSC) properties survive chemotherapy and... (Review)
Review
Glioblastoma remains a tumor with a dismal prognosis because of failure of current treatment. Glioblastoma cells with stem cell (GSC) properties survive chemotherapy and give rise to tumor recurrences that invariably result in the death of the patients. Here we summarize the current knowledge on chemoresistance of malignant glioma with a strong focus on GSC. Chemoresistant GSC are the most likely cause of tumor recurrence, but it remains controversial if GSC and under which conditions GSC are more chemoresistant than non-GSC within the tumor. Regardless of this uncertainty, the chemoresistance varies and it is mainly mediated by intrinsic factors. O6-methyl-guanidine methyltransferase (MGMT) remains the most potent mediator of chemoresistance, but disturbed mismatch repair system and multidrug resistance proteins contribute substantially. However, the intrinsic resistance by MGMT expression is regulated by extrinsic factors like hypoxia increasing MGMT expression and thereby resistance to alkylating chemotherapy. The search of new biomarkers helping to predict the tumor response to chemotherapy is ongoing and will complement the already known markers like MGMT.
Topics: Animals; Antineoplastic Agents, Alkylating; Brain Neoplasms; DNA Mismatch Repair; DNA Modification Methylases; DNA Repair Enzymes; Dacarbazine; Drug Resistance, Neoplasm; Glioma; Humans; Neoplastic Stem Cells; Temozolomide; Tumor Suppressor Proteins
PubMed: 25895710
DOI: 10.1007/978-3-319-16537-0_7 -
Cancer Mar 2017Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation,... (Review)
Review
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas. This clinical review highlights the recent breakthroughs in cancer immunotherapy and the complex correlation of the immune system with primary brain tumors, with special attention to multiple immunotherapy modalities currently being investigated for malignant glioma, including peptide vaccines, dendritic cell vaccines, oncolytic viruses, chimeric T-cell receptors, and checkpoint inhibitors. Cancer 2017;123:734-50. © 2016 American Cancer Society.
Topics: Brain Neoplasms; Chemoradiotherapy; Dendritic Cells; Glioma; Humans; Immunotherapy; Oncolytic Viruses
PubMed: 27875627
DOI: 10.1002/cncr.30371 -
Expert Review of Anticancer Therapy May 2020: Recent discoveries in the molecular makeup of gliomas, the relationship of certain molecular drivers, and the patient's response to therapy and overall prognosis have... (Review)
Review
: Recent discoveries in the molecular makeup of gliomas, the relationship of certain molecular drivers, and the patient's response to therapy and overall prognosis have resulted in a paradigm shift and redefined our understanding of glioma and revealed potential vulnerabilities within this recalcitrant and lethal disease.: We summarize the current classification of malignant glioma in the context of the historical background, current data-driven treatment strategies, and recent discoveries of the mechanisms of pathogenesis of this disease which recapitulates the developing brain. We describe the relationship to common genetic alterations found in glioma, and possible avenues to exploit these newly revealed mechanisms.: Improved understanding of the molecular underpinnings of this disease has been directly translated into treatment decisions and an improved ability to counsel patients regarding their prognosis. We are beginning to see the first glimmer of a return on the investment in regard to immunotherapy in malignant glioma, with further anticipated successful exploitations of the unique pathophysiology of glioma.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immunotherapy; Prognosis
PubMed: 32301635
DOI: 10.1080/14737140.2020.1757440