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Current Treatment Options in Oncology Jul 2020Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a... (Review)
Review
Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a novel, locoregional, antineoplastic treatment modality with favorable efficacy and safety being demonstrated in the most aggressive type of malignant gliomas, glioblastoma (GBM). In 2 large randomized, controlled phase 3 trials, the addition of TTFields was associated with increased overall survival when combined with adjuvant temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM (ndGBM) and comparable overall survival compared with standard chemotherapy in patients with recurrent GBM (rGBM). TTFields target cancer cells by several mechanisms of action (MoA) including suppression of proliferation, migration and invasion, disruption of DNA repair and angiogenesis, antimitotic effects, and induction of apoptosis and immunogenic cell death. Having several MoAs makes TTFields an attractive modality to combine with standard, salvage, and novel treatment regimens (e.g., radiotherapy, chemotherapy, and immunotherapy). Treatment within the field of malignant gliomas is evolving to emphasize combinatorial approaches that work synergistically to improve patient outcomes. Here, we review the current use of TTFields in GBM, discuss MOA and treatment delivery, and consider the potential for its wider adoption in other gliomas.
Topics: Algorithms; Brain Neoplasms; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Factor Analysis, Statistical; Glioblastoma; Glioma; Humans; Radiofrequency Ablation; Treatment Outcome
PubMed: 32734509
DOI: 10.1007/s11864-020-00773-5 -
Cell Mar 2012Eighty percent of malignant tumors that develop in the central nervous system are malignant gliomas, which are essentially incurable. Here, we discuss how recent... (Review)
Review
Eighty percent of malignant tumors that develop in the central nervous system are malignant gliomas, which are essentially incurable. Here, we discuss how recent sequencing studies are identifying unexpected drivers of gliomagenesis, including mutations in isocitrate dehydrogenase 1 and the NF-κB pathway, and how genome-wide analyses are reshaping the classification schemes for tumors and enhancing prognostic value of molecular markers. We discuss the controversies surrounding glioma stem cells and explore how the integration of new molecular data allows for the generation of more informative animal models to advance our knowledge of glioma's origin, progression, and treatment.
Topics: Animals; Brain Neoplasms; Disease Models, Animal; Glioma; Humans; Mice; NF-kappa B; Neoplastic Stem Cells; Signal Transduction
PubMed: 22464322
DOI: 10.1016/j.cell.2012.03.009 -
Seminars in Oncology Nursing Dec 2018To provide an overview of the symptoms commonly experienced by patients with malignant glioma, and discuss the pathophysiology and interventions associated with those. (Review)
Review
OBJECTIVES
To provide an overview of the symptoms commonly experienced by patients with malignant glioma, and discuss the pathophysiology and interventions associated with those.
DATA SOURCES
A review of published scientific literature and clinical literature, and online information from National Comprehensive Cancer Network, Oncology Nursing Society, Epilepsy Foundation of America, and the American Brain Tumor Association.
CONCLUSION
The unique symptom burden associated with a malignant glioma diagnosis often disrupts the lives of patients and their caregivers. Clinical support and interventions addressing malignant glioma-related focal deficits, seizures, headaches, venous thromboembolism, mood disturbances, fatigue, and sleep-wake disturbance can positively impact patient and caregiver experiences while living with malignant glioma.
IMPLICATIONS FOR NURSING PRACTICE
Understanding the pathophysiology of these symptoms and reviewing nursing-led and supported interventions will empower the nurse in providing comprehensive care to patients with malignant glioma and their caregivers.
Topics: Adult; Aged; Aged, 80 and over; Epilepsy; Fatigue; Female; Glioma; Humans; Male; Middle Aged; Oncology Nursing; Practice Guidelines as Topic; Sleep Wake Disorders; Thromboembolism
PubMed: 30424920
DOI: 10.1016/j.soncn.2018.10.014 -
Microscopy Research and Technique Feb 2001Characteristics of human malignant glioma are excessive proliferation, infiltrative growth, angiogenesis and suppression of anti-tumor immune surveillance. Transforming... (Review)
Review
Characteristics of human malignant glioma are excessive proliferation, infiltrative growth, angiogenesis and suppression of anti-tumor immune surveillance. Transforming growth factor-beta (TGF-beta), a versatile cytokine, is intimately involved in the regulation of these processes. Here, we discuss the interactions of TGF-beta with growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet derived growth factor (PDGF), metalloproteinases (MMP-2, MMP-9) and their inhibitor, plasmin activator inhibitor-1 (PAI-1), and immune cells, like natural killer cells, T-cells and microglia. The differential effects of TGF-beta in glioma biology are outlined with emphasis on the induction of a survival advantage for glioma cells by enforced cell growth, migration, invasion, angiogenesis and immune paralysis. By virtue of its growth regulatory and immunomodulatory properties, TGF-beta promises to become a novel target for the experimental therapy of human malignant glioma.
Topics: Brain Neoplasms; Glioma; Humans; Neovascularization, Pathologic; Transforming Growth Factor beta; Tumor Escape
PubMed: 11170299
DOI: 10.1002/1097-0029(20010215)52:4<401::AID-JEMT1025>3.0.CO;2-C -
Critical Reviews in Oncology/hematology Apr 2017Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including... (Review)
Review
BACKGROUND
Coined as the "Warburg effect" and a recognized hallmark of cancer, energy metabolism is aberrantly geared towards aerobic glycolysis in most human cancers, including malignant glioma. Ketogenic metabolic therapy (KMT), i.e. nutritional intervention with ketogenic or low-glycemic diets, has been proposed as an anti-neoplastic strategy in glioma patients.
MATERIALS AND METHODS
We here review the rationale and existing data investigating KMT in management of patients with malignant glioma and discuss the promise and potential challenges of this novel strategy. Results from published clinical studies and ongoing clinical trials on the topic are systematically reviewed, including 6 published original articles and 10 ongoing clinical trials. Search criteria for this review entailed the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar, as well as ICTRP (WHO) and ClinicalTrials.gov (NIH) registries.
RESULTS
A substantial amount of preclinical literature demonstrates KMT efficacy and safety in model systems of malignant glioma. Clinical literature indicates KMT safety and feasibility; 2 clinical studies suggest KMT-associated anti-neoplastic efficacy and clinical benefit. Ongoing clinical trials address KMT safety and metabolic impact, patient compliance, and patient clinical/survival benefit.
CONCLUSIONS
While clinical evidence is still limited in this evolving field, increasing numbers of ongoing clinical trials suggest that KMT is emerging as a potential therapeutic option and might be combinable with existing anti-neoplastic treatments for malignant glioma. Emerging clinical data will help answer questions concerning safety and efficacy of KMT, and are aiming to identify the most promising KMT regimen, compatibility with other anti-cancer treatments, ethical aspects, and impact on quality of life of cancer patients.
Topics: Animals; Diet, Ketogenic; Glioma; Humans
PubMed: 28325264
DOI: 10.1016/j.critrevonc.2017.02.016 -
Journal of UOEH 20205-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a... (Review)
Review
5-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a photosensitizer itself, 5-ALA is a prodrug that accumulates protoporphyrin IX (PpIX) in the mitochondria of glioma cells; PpIX acts as a photosensitizer. Fluorescence-guided resection for malignant gliomas has some pitfalls. Moreover, 5-ALA is not merely a fluorescence marker but has potential as a mitochondria-targeting drug for malignant glioma therapy. In this article, we review the literature related to 5-ALA, discuss the pitfalls of fluorescence-guided resection using 5-ALA for malignant gliomas, and describe the application of 5-ALA for malignant glioma therapy with personal opinions.
Topics: Aminolevulinic Acid; Brain Neoplasms; Fluorescence; Glioma; Humans; Mitochondria; Photosensitizing Agents; Protoporphyrins; Reactive Oxygen Species; Surgery, Computer-Assisted
PubMed: 32213740
DOI: 10.7888/juoeh.42.27 -
Current Oncology Reports Nov 2017Cancers are "reprogrammed" to use a much higher rate of glycolysis (GLY) relative to oxidative phosphorylation (OXPHOS), even in the presence of adequate amounts of... (Review)
Review
Cancers are "reprogrammed" to use a much higher rate of glycolysis (GLY) relative to oxidative phosphorylation (OXPHOS), even in the presence of adequate amounts of oxygenation. Originally identified by Nobel Laureate Otto Warburg, this hallmark of cancer has recently been termed metabolic reprogramming and represents a way for the cancer tissue to divert carbon skeletons to produce biomass. Understanding the mechanisms that underlie this metabolic shift should lead to better strategies for cancer treatments. Malignant gliomas, cancers that are very resistant to conventional treatments, are highly glycolytic and seem particularly suited to approaches that can subvert this phenotype.
Topics: Glioma; Glycolysis; Humans; Metabolism; Oxidative Phosphorylation
PubMed: 29098465
DOI: 10.1007/s11912-017-0637-y -
Seminars in Cancer Biology Jan 2021Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases... (Review)
Review
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Discovery; Drug Repositioning; Glioma; Humans
PubMed: 31734137
DOI: 10.1016/j.semcancer.2019.10.018 -
Annals of Oncology : Official Journal... May 2009
Review
Topics: Brain Neoplasms; Europe; Follow-Up Studies; Glioma; Health Planning Guidelines; Humans; Societies, Medical; Treatment Outcome
PubMed: 19454432
DOI: 10.1093/annonc/mdp151 -
Neurosurgery Clinics of North America Jan 1990The many options neurologic surgeons have for the treatment of malignant gliomas are reviewed. Although virtually no malignant gliomal tumor can be cured by surgical... (Review)
Review
The many options neurologic surgeons have for the treatment of malignant gliomas are reviewed. Although virtually no malignant gliomal tumor can be cured by surgical resection alone, in the majority of cases, some combination of open resection or stereotactic surgery can produce a diagnosis, ameliorate symptoms, decrease the intracranial pressure, improve neurologic status, remove most of the tumor, and deliver other therapeutic agents. The techniques of both open resection and stereotactic surgery are discussed.
Topics: Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Stereotaxic Techniques; Survival Rate
PubMed: 2135973
DOI: No ID Found