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Cancer Jul 2007Malignant gliomas are relatively uncommon but lethal cancers. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant gliomas has... (Review)
Review
Malignant gliomas are relatively uncommon but lethal cancers. Despite recent research efforts in cancer therapy, the prognosis of patients with malignant gliomas has remained dismal. Understanding the molecular pathogenesis of glioma may lead to a rational development of new therapies. Despite the genetic heterogeneity of malignant gliomas, common aberrations in the signaling elements of the growth and survival pathways are found. New treatments have emerged to target molecules in these signaling pathways with the goal to increase specific efficacy and minimize toxicity. Monoclonal antibodies and low molecular-weight kinase inhibitors are the most common classes of agents in targeted cancer treatment. Most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit in unselected malignant glioma patient populations. Several mechanisms of treatment failure have been demonstrated. In response, multitargeted kinase inhibitors and combinations of single-targeted kinase inhibitors have been developed to overcome therapeutic resistance. In addition, multimodality combinations of targeted agents with radiation, chemotherapy, or immunotherapy/vaccines may enhance treatment efficacy. Future development of these agents will require advances in discovery and validation of new molecular targets, improvement of therapeutic delivery, and identification of correlative biomarkers. Novel clinical trial designs and endpoints may increase the efficiency of new drug evaluation. In this review, the authors discussed the current understanding of molecular pathogenesis and the development of molecularly targeted therapies in malignant glioma.
Topics: Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Intercellular Signaling Peptides and Proteins; Models, Biological; Receptors, Growth Factor; Signal Transduction
PubMed: 17520692
DOI: 10.1002/cncr.22741 -
Expert Opinion on Biological Therapy Aug 2019With the approval of talimogene laherparepvec (T-VEC) for advanced malignant melanoma, virotherapy using oncolytic herpes simplex virus (oHSV) is now emerging as a... (Review)
Review
INTRODUCTION
With the approval of talimogene laherparepvec (T-VEC) for advanced malignant melanoma, virotherapy using oncolytic herpes simplex virus (oHSV) is now emerging as a viable therapeutic option for cancer patients, including malignant gliomas.
AREAS COVERED
This review summarizes the most recent literature to provide cutting-edge knowledge about preclinical and clinical development of oHSV therapy for malignant gliomas, presenting current approaches to overcome obstacles to successful clinical application of oHSV in neuro-oncology.
EXPERT OPINION
Current strategies to improve the efficacy of oHSV therapy include engineering new viruses, modulation of innate and adaptive immune responses, combination with other treatments, and developing new oHSV delivery. All of these could rapidly be translated into clinical investigations, following several clinical trials that are currently ongoing.
Topics: Animals; Clinical Trials as Topic; Glioma; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus
PubMed: 31046478
DOI: 10.1080/14712598.2019.1614557 -
Current Neurology and Neuroscience... Jul 2010Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful,... (Review)
Review
Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research led to several clinical trials based on tumor immunotherapy to treat patients with malignant glioma. Here we review 17 recent glioma immunotherapy clinical trials, published over the past 3 years. Various approaches were used, including passive transfer of naked and radiolabeled antibodies, tumor antigen-specific peptide immunization, and the use of patient tumor cells with or without dendritic cells as vaccines. We compare and discuss the current state of the art of clinical immunotherapy treatment, as well as its limited successes, pitfalls, and future potential.
Topics: Brain Neoplasms; Clinical Trials as Topic; Glioma; Immunotherapy; Treatment Outcome
PubMed: 20424975
DOI: 10.1007/s11910-010-0111-9 -
Current Neurology and Neuroscience... Feb 2016Malignant gliomas are intractable and among the most lethal human malignancies. Like other cancers, metabolic reprogramming is a key feature of glioma and is thought to... (Review)
Review
Malignant gliomas are intractable and among the most lethal human malignancies. Like other cancers, metabolic reprogramming is a key feature of glioma and is thought to accommodate the heightened nutrient requirements for tumor cell proliferation, growth, and survival. This metabolic rewiring, driven by oncogenic signaling and molded by the unique environment of the brain, may impose vulnerabilities that could be exploited therapeutically for increased tumor control. In this review, we discuss the prominent metabolic features of malignant glioma, the key pathways regulating glioma metabolism, and the potential therapeutic opportunities for targeting metabolic processes.
Topics: Brain; Glioma; Humans; Signal Transduction
PubMed: 26759318
DOI: 10.1007/s11910-015-0613-6 -
Neuroscience Bulletin Feb 2008The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier,... (Review)
Review
The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier, the absence of lymphatic tissues and dendritic cells (DCs) in the central nervous system (CNS) parenchyma, and the presence of an immunosuppressive microenvironment. Therefore, immunotherapeutic approaches will not be beneficial unless the compromised immune status in malignant glioma patients is overcome. DC-based immunotherapy, vaccinating cancer patients with DCs pulsed with various tumor antigens, is one of the most promising immunotherapeutic approaches for treatment of malignant glioma because it seems able to overcome, at least partially, the immunosuppressive state associated with primary malignancies. The preparation of DCs, choice of antigen, and route and schedule of administration are improving and optimizing with rapid development of molecular biology and gene engineering technology. DC vaccination in humans, after a number of pre-clinical models and clinical trials, would increase the clinical benefits for malignant glioma immunotherapy.
Topics: Dendritic Cells; Glioma; Humans; Immunotherapy
PubMed: 18273075
DOI: 10.1007/s12264-008-1107-1 -
Neuro-oncology Mar 2016The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome... (Review)
Review
The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA measures that are feasible and have appropriate psychometric properties for use in this patient population as well as highlight where further development is needed.
Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Outcome Assessment, Health Care; Quality of Life; Surveys and Questionnaires
PubMed: 26989128
DOI: 10.1093/neuonc/nov291 -
Cancer Immunology, Immunotherapy : CII Feb 2011Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered... (Review)
Review
Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered promising, it is clear that immunotherapy does not on its own represent the magic bullet in glioma therapy. In this review, we summarize the major immunotherapeutic achievements in the mouse GL261 glioma model, which has emerged as the gold standard syngeneic model for experimental glioma therapy. Gene therapy, monoclonal antibody treatment, cytokine therapy, cell transfer strategies and dendritic cell therapy were hereby considered. Apart from the considerable progress made in understanding glioma immunology in this model, we also addressed its most pertinent issues and shortcomings. Despite these, the GL261 model will remain indispensable in glioma research since it is a fast, highly reproducible and easy-to-establish model system.
Topics: Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Immunotherapy; Mice; Neoplasms, Experimental
PubMed: 21120655
DOI: 10.1007/s00262-010-0946-6 -
Neurological Research Oct 2005Traditional therapies for the treatment of malignant glioma have failed to make appreciable gains regarding patient outcome in the last decade. Therefore,... (Review)
Review
Traditional therapies for the treatment of malignant glioma have failed to make appreciable gains regarding patient outcome in the last decade. Therefore, immunotherapeutic approaches have become increasingly popular in the treatment of this cancer. This article reviews general immunology of the central nervous system and the immunobiology of malignant glioma to provide a foundation for understanding the rationale behind current glioma immunotherapies. A review of currently implemented immunological treatments is then provided with special attention paid to the use of vaccines, gene therapy, cytokines, dendritic cells and viruses. Insights into future and developing avenues of glioma immunotherapy, such as novel delivery systems, are also discussed.
Topics: Animals; Brain; Cytokines; Dendritic Cells; Disease Models, Animal; Glioma; Humans; Immunotherapy; Spinal Cord
PubMed: 16197807
DOI: 10.1179/016164105X49481 -
Journal of Neuro-oncology Apr 2014Gathering evidence has revealed that Akt signaling pathway plays an important role in glioma progression and aggressiveness. Among Akt kinases the most studied, Akt1,... (Review)
Review
Gathering evidence has revealed that Akt signaling pathway plays an important role in glioma progression and aggressiveness. Among Akt kinases the most studied, Akt1, has been involved in many cellular processes that are in favor of cell malignancy. More recently, the actions of the two other isoforms, Akt2 and Akt3 have emerged in glioma. After a description of Akt pathway activation, we will explore the role of each isoform in malignant glioma that strengthens the current preclinical and clinical studies evaluating the impact of Akt pathway targeting in glioblastomas.
Topics: Carcinogenesis; Disease Progression; Drug Resistance, Neoplasm; Enzyme Activation; Glioma; Humans; Isoenzymes; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 24477623
DOI: 10.1007/s11060-014-1382-9 -
Current Neurology and Neuroscience... Jun 2017Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this... (Review)
Review
PURPOSE OF REVIEW
Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses.
RECENT FINDINGS
Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.
Topics: Adoptive Transfer; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Humans; Immunotherapy; Oncolytic Viruses
PubMed: 28488122
DOI: 10.1007/s11910-017-0754-x