Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Current Options and Future Directions in Immune Therapy for Glioblastoma.

ABSTRACT: Glioblastoma is in need of innovative treatment approaches. Immune therapy for cancer refers to the use of the body's immune system to target malignant cells in the body. Such immune therapeutics have recently been very successful in treating a diverse group of cancerous lesions. As a result, many new immune therapies have gained Food and Drug Administration approval for the treatment of cancer, and there has been an explosion in the study of immune therapeutics for cancer treatment over the past few years. However, the immune suppression of glioblastoma and the unique immune microenvironment of the brain make immune therapeutics more challenging to apply to the brain than to other systemic cancers. Here, we discuss the existing barriers to successful immune therapy for glioblastoma and the ongoing development of immune therapeutics. We will discuss the discovery and classification of immune suppressive factors in the glioblastoma microenvironment; the development of vaccine-based therapies; the use of convection-enhanced delivery to introduce tumoricidal viruses into the tumor microenvironment, leading to secondary immune responses; the emerging use of adoptive cell therapy in the treatment of glioblastoma; and future frontiers, such as the use of cerebral microdialysis for immune monitoring and the use of sequencing to develop patient-specific therapeutics. Armed with a better understanding of the challenges inherent in immune therapy for glioblastoma, we may soon see more successes in immune-based clinical trials for this deadly disease.

SUBMITTER: Lynes J

PROVIDER: S-EPMC6290347 | biostudies-other | 2018

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Tumour treating fields therapy for glioblastoma: current advances and future directions.

Project description:Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.

| S-EPMC7884384 | biostudies-literature

Current Options and Future Directions for NAFLD and NASH Treatment.

Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although there are many undergoing clinical trials for NAFLD treatment, there is no currently approved treatment. NAFLD accounts as a major causing factor for the development of hepatocellular carcinoma (HCC), and its incidence rises accompanying the prevalence of obesity and diabetes. Reprogramming of antidiabetic and anti-obesity medicine is a major treatment option for NAFLD and NASH. Liver inflammation and cellular death, with or without fibrosis account for the progression of NAFLD to NASH. Therefore, molecules and signaling pathways involved in hepatic inflammation, fibrosis, and cell death are critically important targets for the therapy of NAFLD and NASH. In addition, the avoidance of aberrant infiltration of inflammatory cytokines by treating with CCR antagonists also provides a therapeutic option. Currently, there is an increasing number of pre-clinical and clinical trials undergoing to evaluate the effects of antidiabetic and anti-obesity drugs, antibiotics, pan-caspase inhibitors, CCR2/5 antagonists, and others on NAFLD, NASH, and liver fibrosis. Non-invasive serum diagnostic markers are developed for fulfilling the need of diagnostic testing in a large amount of NAFLD cases. Overall, a better understanding of the underlying mechanism of the pathogenesis of NAFLD is helpful to choose an optimized treatment.

| S-EPMC8306701 | biostudies-literature

Emerging therapies for glioblastoma: current state and future directions.

Project description:Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given the poor survival with currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment in basic science of glioblastoma are rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling of glioblastoma as well as the brain microenvironment and immune system interactions. Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. In addition, techniques to overcome the blood-brain barrier (BBB) for targeted delivery are being tested in clinical trials in patients with recurrent GBM. Here, we set forth the rationales for these promising therapies in treating GBM, review the potential novel agents, the current status of preclinical and clinical trials, and discuss the challenges and future perspectives in glioblastoma immuno-oncology.

| S-EPMC9013078 | biostudies-literature

Anti-inflammatory and immune therapy for Alzheimer's disease: current status and future directions.

Project description:From the initial characterizations of inflammatory responses in Alzheimer's disease (AD) affected brains, namely the demonstration of activated microglia and reactive astrocytes, complement system activation, increased production of proinflammatory cytokines, and evidence for microglial-produced neurotoxins, there was hope that reducing inflammation might be a feasible treatment for this memory-robbing disease. This hope was supported by a number of epidemiology studies demonstrating that patients who took non-steroidal anti-inflammatory drugs had significantly lower risk of developing AD. However, clinical trials of anti-inflammatories have not shown effectiveness, and in recent years, the concept of immune therapy has become a treatment option as animal studies and clinical trials with Abeta vaccines have demonstrated enhanced amyloid removal through stimulation of microglial phagocytosis.This review will examine the current status of whether inhibiting inflammation is a valid therapeutic target for treating AD; what lessons have come from the clinical trials; what new pathways and classes of agents are being considered; and how this field of research can progress towards new therapeutics. We will examine a number of agents that have shown effectiveness in reducing inflammation amongst other demonstrated mechanisms of action. The major focus of much AD drug discovery has been in identifying agents that have anti-amyloid properties; however, a number of these agents were first identified for their anti-inflammatory properties. As drug development and clinical testing is a costly and lengthy endeavor, sound justification of new therapeutic targets is required. Possible future directions for AD anti-inflammatory or immune clearance therapy will be discussed based on recent experimental data.

| S-EPMC2644496 | biostudies-other

Bevacizumab for glioblastoma: current indications, surgical implications, and future directions.

Project description:Initial enthusiasm after promising Phase II trials for treating recurrent glioblastomas with the antiangiogenic drug bevacizumab—a neutralizing antibody targeting vascular endothelial growth factor—was tempered by recent Phase III trials showing no efficacy for treating newly diagnosed glioblastomas. As a result, there is uncertainty about the appropriate indications for the use of bevacizumab in glioblastoma treatment. There are also concerns about the effects of bevacizumab on wound healing that neurosurgeons must be aware of. In addition, biochemical evidence suggests a percentage of tumors treated with bevacizumab for an extended period of time will undergo transformation into a more biologically aggressive and invasive phenotype with a particularly poor prognosis. Despite these concerns, there remain numerous examples of radiological and clinical improvement after bevacizumab treatment, particularly in patients with recurrent glioblastoma with limited therapeutic options. In this paper, the authors review clinical results with bevacizumab for glioblastoma treatment to date, ongoing trials designed to address unanswered questions, current clinical indications based on existing data, neurosurgical implications of bevacizumab use in patients with glioblastoma, the current scientific understanding of the tumor response to short- and long-term bevacizumab treatment, and future studies that will need to be undertaken to enable this treatment to fulfill its therapeutic promise for glioblastoma.

| S-EPMC4839778 | biostudies-literature

Second-line treatment of metastatic gastric cancer: Current options and future directions.

Project description:Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.

| S-EPMC4631965 | biostudies-other

Management of cutaneous neurofibroma: current therapy and future directions.

Project description:Neurofibromatosis type 1 (NF1) is a life-long neurocutaneous disorder characterized by a predisposition to tumor development, including cutaneous neurofibroma (cNF), the hallmark of the disease. cNF is a histologically benign, multicellular tumor formed in virtually most individuals with NF1. It is considered the most burdensome feature of the disorder due to their physical discomfort, cosmetically disfiguring appearance, and psychosocial burden. Management of cNF remains a challenge in the medical field. Effective medicinal treatment for cNF does not exist at this time. Trials aimed at targeting individual components of the neoplasm such as mast cells with Ketotifen have not shown much success. Physical removal or destruction has been the mainstay of therapy. Surgical removal gives excellent cosmetic results, but risk in general anesthesia may require trained specialists. Destructive laser such as CO2 laser is effective in treating hundreds of tumors at one time but has high risk of scarring hypopigmentation or hyperpigmentation that alter cosmetic outcomes. A robust, low-risk surgical technique has been developed, which may be performed in clinic using traditional biopsy tools that may be more accessible to NF1 patients worldwide than contemporary techniques including Er:YAG or Nd:YAG laser. In this review, specific recommendations for management of cNFs are made based on symptoms, clinical expertise, and available resources. Additionally, antiproliferative agents aimed at stimulating cellular quiescence are explored.

| S-EPMC7317049 | biostudies-literature

Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions.

Project description:Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent in vitro, in vivo, and pre-clinical studies.

| S-EPMC7681102 | biostudies-literature

Current therapy and future directions in biliary tract malignancies.

Project description:Cancers of the biliary tree represent a rare group of diseases with a devastating impact on patients. Gallbladder cancer often is associated with cholelithiasis. Cholangiocarcinoma may arise in the setting of biliary inflammation, such as primary sclerosing cholangitis, but most commonly occurs in patients without a particular risk factor. Surgical removal of biliary cancer is essential for cure, but it is associated with a very high rate of recurrence and for many patients is not possible at the time of diagnosis. Although risk factors differ for each anatomic site, systemic treatment is generally similar. Various adjunctive therapies, such as radiation and embolization, have been investigated for biliary tract cancers with modest success and efforts are ongoing to understand how to optimize these tools. Retrospective series and pooled analysis suggest a benefit for adjuvant treatment following resection, but prospective data are limited. Ongoing and planned phase 3 trials should help to clarify the role of adjuvant chemotherapy and radiation. For advanced disease, chemotherapy improves quality of life and survival, and gemcitabine with cisplatin represents the standard of care. However, all patients ultimately progress on this therapy, so clinical trials of new and better agents are essential to expand the existing treatment options for patients.

| S-EPMC3769474 | biostudies-other

Neoadjuvant therapy for gastric cancer: current evidence and future directions.

Project description:Although surgical resection remains the only potentially curative treatment for gastric cancer (GC), poor long-term outcomes with resection alone compel a multimodality approach to this disease. Multimodality strategies vary widely; while adjuvant approaches are typically favored in Asia and the United States (USA), a growing body of evidence supports neoadjuvant and/or perioperative strategies in locally advanced tumors. Neoadjuvant approaches are particularly attractive given the morbidity associated with surgical management of GC and the substantial risk of omission of adjuvant therapy. The specific advantages of chemoradiotherapy (CRT) compared to chemotherapy have not been well defined, particularly in the preoperative setting and trials aimed at determining the optimal elements and sequencing of therapy are underway. Future studies will also define the role of targeted and biologic therapies.

| S-EPMC4570921 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data