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Frontiers in Immunology 2020Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Glioblastoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Immunotherapy, Adoptive; Molecular Targeted Therapy; Oncolytic Virotherapy; Treatment Outcome; Tumor Microenvironment
PubMed: 33767690
DOI: 10.3389/fimmu.2020.603911 -
Pharmacology 2023Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment... (Review)
Review
BACKGROUND
Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death.
SUMMARY
In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM.
KEY MESSAGES
This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.
Topics: Humans; Glioblastoma; Glioma; Oncolytic Virotherapy; Temozolomide; Brain Neoplasms
PubMed: 37459849
DOI: 10.1159/000531319 -
International Journal of Oncology Jun 2022Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and is associated with a poor clinical prognosis. Despite the progress in the... (Review)
Review
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and is associated with a poor clinical prognosis. Despite the progress in the understanding of the molecular and genetic changes that promote tumorigenesis, effective treatment options are limited. The present review intended to identify and summarize major signaling pathways and genetic abnormalities involved in the pathogenesis of GBM, as well as therapies that target these pathways. Glioblastoma remains a difficult to treat tumor; however, in the last two decades, significant improvements in the understanding of GBM biology have enabled advances in available therapeutics. Significant genomic events and signaling pathway disruptions (NF‑κB, Wnt, PI3K/AKT/mTOR) involved in the formation of GBM were discussed. Current therapeutic options may only marginally prolong survival and the current standard of therapy cures only a small fraction of patients. As a result, there is an unmet requirement for further study into the processes of glioblastoma pathogenesis and the discovery of novel therapeutic targets in novel signaling pathways implicated in the evolution of glioblastoma.
Topics: Brain Neoplasms; Glioblastoma; Humans; Phosphatidylinositol 3-Kinases; Signal Transduction; Treatment Outcome
PubMed: 35445737
DOI: 10.3892/ijo.2022.5359 -
EMBO Molecular Medicine Nov 2014Glioblastoma multiforme (GBM) is the deadliest form of brain tumor with a more than 90% 5-year mortality. GBM has a paltry median survival of 12.6 months attributed to... (Review)
Review
Glioblastoma multiforme (GBM) is the deadliest form of brain tumor with a more than 90% 5-year mortality. GBM has a paltry median survival of 12.6 months attributed to the unique treatment limitations such as the high average age of onset, tumor location, and poor current understandings of the tumor pathophysiology. The resection techniques, chemotherapic strategies, and radiation therapy currently used to treat GBM have slowly evolved, but the improvements have not translated to marked increases in patient survival. Here, we will discuss the recent progress in our understanding of GBM pathophysiology, and the diagnostic techniques and treatment options. The discussion will include biomarkers, tumor imaging, novel therapies such as monoclonal antibodies and small-molecule inhibitors, and the heterogeneity resulting from the GBM cancer stem cell population.
Topics: Biomedical Research; Brain Neoplasms; Glioblastoma; Humans; Immunotherapy
PubMed: 25312641
DOI: 10.15252/emmm.201302627 -
Asian Pacific Journal of Cancer... Sep 2018Introduction: To evaluate the survival of Glioblastoma Multiforme (GBM). Material and Methods: Patients with a pathological diagnosis of Glioblastoma Multiforme (GBM)...
Introduction: To evaluate the survival of Glioblastoma Multiforme (GBM). Material and Methods: Patients with a pathological diagnosis of Glioblastoma Multiforme (GBM) between 1 January 1994 and 30 November 2013, were retrospectively reviewed. Inclusion criteria: 1) GBM patients with confirmed pathology, 2) GBM patients were treated by multimodality therapy. Exclusion criteria: 1) GBM patients with unconfirmed pathology, 2) GBM patients with spinal involvement, 3) GBM patients with incomplete data records. Seventy-seven patients were treated by multimodality therapy such as surgery plus post-operative radiotherapy (PORT), post-operative Temozolomide (TMZ) concurrent with radiotherapy (CCRT), post-operative CCRT with adjuvant TMZ. The overall survival was calculated by the Kaplan-Meier method and the log-rank test was used to compare the survival curves. A p-value of ≤ 0.05 was considered to be statistically significant. Results: Seventy-seven patients with a median age of 53 years (range 4-76 years) showed a median survival time (MST) of 12 months. In subgroup analyses, the PORT patients revealed a MST of 11 months and 2 year overall survival (OS) rates were 17.2%, the patients with post-operative CCRT with or without adjuvant TMZ revealed a MST of 23 months and 2 year OS rates were 38.2%. The MST of patients by Recursive Partitioning Analysis (RPA), classifications III, IV, V, VI were 26.8 months, 14.2 months, 9.9 months, and 4.0 months, (p <0.001). Conclusions: The MST of the patients who had post-operative CCRT with or without adjuvant TMZ was better than the PORT group. The RPA classification can be used to predict survival. Multimodality therapy demonstrated the most effective treatment outcome. Temozolomide might be beneficial for GBM patients in order to increase survival time.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Chemoradiotherapy; Child; Child, Preschool; Female; Follow-Up Studies; Glioblastoma; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 30256068
DOI: 10.22034/APJCP.2018.19.9.2613 -
Cells Jun 2022Glioblastoma (GBM, grade IV astrocytoma), the most frequently occurring primary brain tumor, presents unique challenges to therapy due to its location, aggressive...
Glioblastoma (GBM, grade IV astrocytoma), the most frequently occurring primary brain tumor, presents unique challenges to therapy due to its location, aggressive biological behavior, and diffuse infiltrative growth, thus contributing to having disproportionately high morbidity and mortality [...].
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Humans; Molecular Biology
PubMed: 35681545
DOI: 10.3390/cells11111850 -
Nature Medicine Jan 2020Immune checkpoint therapy with anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatment of many solid tumors. However, the clinical efficacy of immune checkpoint...
Immune checkpoint therapy with anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatment of many solid tumors. However, the clinical efficacy of immune checkpoint therapy is limited to a subset of patients with specific tumor types. Multiple clinical trials with combinatorial immune checkpoint strategies are ongoing; however, the mechanistic rationale for tumor-specific targeting of immune checkpoints is elusive. To garner an insight into tumor-specific immunomodulatory targets, we analyzed 94 patients representing five different cancer types, including those that respond relatively well to immune checkpoint therapy and those that do not, such as glioblastoma multiforme, prostate cancer and colorectal cancer. Through mass cytometry and single-cell RNA sequencing, we identified a unique population of CD73 macrophages in glioblastoma multiforme that persists after anti-PD-1 treatment. To test if targeting CD73 would be important for a successful combination strategy in glioblastoma multiforme, we performed reverse translational studies using CD73 mice. We found that the absence of CD73 improved survival in a murine model of glioblastoma multiforme treated with anti-CTLA-4 and anti-PD-1. Our data identified CD73 as a specific immunotherapeutic target to improve antitumor immune responses to immune checkpoint therapy in glioblastoma multiforme and demonstrate that comprehensive human and reverse translational studies can be used for rational design of combinatorial immune checkpoint strategies.
Topics: 5'-Nucleotidase; Algorithms; Animals; Brain Neoplasms; Cell Line, Tumor; Disease Models, Animal; GPI-Linked Proteins; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Macrophages; Magnetic Resonance Imaging; Mice, Inbred C57BL; Molecular Targeted Therapy; Myeloid Cells
PubMed: 31873309
DOI: 10.1038/s41591-019-0694-x -
Cancer Medicine Aug 2016Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment.
Topics: Animals; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Genetic Therapy; Glioblastoma; Humans; MicroRNAs; RNA Interference
PubMed: 27282910
DOI: 10.1002/cam4.775 -
Frontiers in Immunology 2024
Topics: Humans; Glioblastoma; Immunotherapy; Brain Neoplasms; Immune Checkpoint Inhibitors; Treatment Outcome; Animals
PubMed: 38715607
DOI: 10.3389/fimmu.2024.1407930 -
BioMed Research International 2014
Topics: Brain Neoplasms; Glioblastoma; Humans
PubMed: 25587536
DOI: 10.1155/2014/432195