Preclinical research from The University of Texas MD Anderson Cancer Center finds that although glioblastoma stem cells (GSCs) can be targeted by natural killer (NK) cells, they are able to evade immune attack by releasing the TFG-β signaling protein, which blocks NK cell activity. Deleting the TFG-β receptor in NK cells, however, rendered them resistant to this immune suppression and enabled their anti-tumor activity.
CAR-T-mediated immunotherapy for glioblastoma multiforme. The broad categories of immunotherapy include cancer vaccines, checkpoint inhibitors, oncolytic virus therapies, and chimeric antigen receptor (CAR) functionalized immune cell therapies. In this short chapter, we provide a brief view of the cell-based immunotherapy developed for GBM, with a focus on CAR-T cells.
The Company has received approval from the Israeli Ministry of Health to begin the Phase 1/2 portion of its study of its lead asset, EV101, designed to investigate the safety and efficacy of synthetic cannabidiol (CBD) when administered alone or in combination with clomiphene, concurrently with temozolomide, to treat patients suffering from recurrent or progressive glioblastoma (GBM). The study will be conducted at the Davidoff Institute of Oncology, Rabin Medical Center, in Israel under Principal Investigator Dr. Tali Siegal.
Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis.
As Glioblastoma (GBM) Awareness Day approaches, we recognize that glioblastoma multiforme (GBM) is a challenging indication that has not received any new approved therapies in well over a decade. New innovations are creating opportunities for therapeutic research, and Worldwide Clinical Trials is poised to support development in GBM treatments. In this short video, Alaeddin Homsi, MS, BS, Executive Director for Oncology Project Management, discusses Worldwide’s increasing commitment to oncology research and its recent work supporting GBM studies, in particular.
In this review, we explore the mechanisms by which cancer cells, and especially GBM, can acquire resistance to treatment. We describe and discuss the concept of persister/tolerant cells that precede and/or accompany the acquisition of resistance. Persister/tolerant cells are cancer cells that are not eliminated by treatment(s) because of different mechanisms ranging from dormancy/quiescence to senescence. We discuss the possibility of targeting these mechanisms in new therapeutic regimen.
Early symptoms of brain tumours in adults are non-specific, and patients may present multiple times to primary care services before they are referred for investigation. Look for symptoms of raised intracranial pressure (such as headaches exacerbated by lying down, triggered by the Valsalva manoeuvre, or associated with vomiting or visual disturbance), combinations of symptoms (such as headache plus cognitive impairment, headache plus weakness, headache plus personality change), and symptoms that progress over time. New onset focal or generalised seizures in adulthood also warrant investigation for a brain tumour.
Twenty Nine Years ago, Yacobus Fitriyadi Kusdinata was diagnosed with a Glioblastoma Multiforme. He feels strongly that the best medication for him was not chemotherapy nor radiotherapy but exercise. “It has been over 19 years since my diagnosis. I feel great, I am healthy, I don’t take any medication, I just jog 15 km three times weekly”. – Yacobus Fitriyadi Kusdinata
Unlike other brain tumors that start in the body and spread to the brain, glioblastoma starts in the brain or spinal cord. Primary brain tumors are relatively rare, with fewer than 25,000 Americans diagnosed with them each year. Metastasized tumors, however, are more prevalent and an estimated 400,000 are diagnosed in the United States each year.
Houston Methodist Neurological Institute researchers from the department of neurosurgery shrunk a deadly glioblastoma tumor by more than a third using a helmet generating a noninvasive oscillating magnetic field that the patient wore on his head while administering the therapy in his own home. The 53-year-old patient died from an unrelated injury about a month into the treatment, but during that short time, 31% of the tumor mass disappeared. The autopsy of his brain confirmed the rapid response to the treatment.
Reactive oxygen and nitrogenous sources include endogenous (physiological processes), and exogenous sources contain reactive oxygen and nitrogen (xenobiotic interaction). The cellular oxidation/reduction shifts to oxidative stress when the regulation mechanisms of antioxidants are surpassed, and this raises the ability to damage cellular lipids, proteins, and nucleic acids.
Nanomaterials found in consumer and health-care products can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape - creating potential neurological impacts that could be both positive and negative, a new study reveals.
The Ivy Brain Tumor Center at Barrow Neurological Institute, a nonprofit translational research program, is conducting a Phase 0, first-in-human clinical trial of sonodynamic therapy (SDT) in ascending energy doses to assess safety and efficacy in patients with recurrent high-grade glioma. In this study, sonodynamic therapy is the combination of the drug SONALA-001 (5-ALA, aminolevulinic acid HCl, or ALA) and a Magnetic Resonance-Guided Focused Ultrasound device called the Exablate 4000 Type-2 Device. The goal of this study is to assess biological changes (tumor cell death) associated with the sonodynamic therapy.
Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the “expected residual tumor volume” (eRV) and the “expected resectability index” (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined.
Glioblastoma (GBM), while still considered a rare cancer, is the most common malignant primary brain tumor in adults, accounting for 54% of all gliomas and 16% of all primary brain tumors. GBM is one of the most aggressive cancers - the median age of diagnosis is 64 years and the 5-year relative survival rate in patients afed 55 to 64 years is just 6%, according to the American Cancer Society.1,2
Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system (CNS). However, current GBM treatments are ineffective, signifying the great importance of exploring new therapeutic targets. Curcumin has been found to be a natural compound with an anticancer potential. However, its targets and mechanisms in GBM are still unclear.
For decades the dominant approach to understanding the brain has been to measure how many times individual neurons activate during particular behaviors. In contrast to this “rate code,” a more recent hypothesis proposes that neurons signal information by changing the precise timing when they activate.
Although the biology of glioblastoma multiforme has recently been widely investigated, the studies summarizing the knowledge of its development and treatment are still not sufficient in terms of comprehensive brain tumor analysis.
Glioblastoma (GBM) is the most common malignant brain tumor in adults. The prognosis of GBM patients is poor. Even with active standard treatment, the median overall survival is only 14.6 months. It is therefore critical to ascertain recurrence and search for factors that influence the prognosis of GBM. This study aimed to screen the variables related to the progression-free survival (PFS) and overall survival (OS) of GBM patients undergoing surgery and concurrent chemoradiotherapy, as well as propose a nomogram for individual risk prediction based on preoperative imaging parameters and clinicopathological variables readily available in clinical practice.
Adult Glioblastoma is a highly aggressive malignant brain tumor. Although numerous mechanistic studies have revealed and underlined the unique behavior of Glioblastoma, still, only a few chemotherapeutics are used for its treatment. The standard procedure, which has not been modified in the last two decades, includes surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy. Unfortunately, glioblastoma recurrence is extremely frequent, and the median patient survival remains 15 to 18 months from diagnosis. Problems with the introduction of new therapies, even as adjuvants, include the low penetration of anticancer drugs in the brain due to the blood–brain barrier, the high inter- and intra-tumor heterogeneity of glioblastoma cells, as well as their invasiveness and resistance to therapy. Many promising targeted therapies based on preclinical studies failed to prolong glioblastoma patient survival and the stagnation implementing new therapeutic strategies is evident. Therefore, new glioblastoma models that will improve our knowledge and allow investigation of new therapeutic strategies under conditions that mimic the situation in patients with high fidelity are demanded.
DE-RT alone resulted in superior PFS and OS vs. SoC-RT alone. DE-RT+TMZ did not lead to improved outcomes vs. SoC-RT+TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.
Oncolytic viruses have attracted widespread attention as biological anticancer agents that can selectively kill tumor cells without affecting normal cells. Although progress has been made in therapeutic strategies, the prognosis of patients with glioblastoma (GBM) remains poor and no ideal treatment approach has been developed. Recently, oncolytic herpes simplex virus (oHSV) has been considered a promising novel treatment approach for GBM.
CAR-T therapies that use engineered versions of patients' own immune cells to recognize cancer antigens have shown great efficacy in certain blood cancers. But they’ve been largely ineffective against solid tumors because of a lack of tumor-specific antigens and the tendency of CAR-Ts to wither in an immunosuppressive tumor microenvironment.
So far, the Beijing-based research has been conducted only in animal models, but the research is a tantalizing step toward a new form of CAR T cell therapy for solid tumors, the subject of a worldwide race in recent years. The current form of treatment is composed of specially endowed cells that are engineered to destroy cancers of the blood. The emerging form of therapy promises the same powerful action—killing cancer cells, but this time from solid tumors while leaving healthy tissue unscathed.
The importance of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status as a predictive factor for the response to chemotherapy with temozolomide is well established. Its significance though at stratifying glioblastoma (GBM) patients in regard to their prognostic factors and the impact of surgical approach on them has not been identified.
Despite access to some of the best possible medical care in the world, Senators John McCain and Edward Kennedy both died within 18 months of their diagnosis of glioblastoma, an aggressive form of brain cancer. While this deadly outcome typifies the nature of this disease, some glioblastoma patients see exceptional benefits from chemotherapy and survive beyond expectations. Why this happens has been revealed by researchers at the University of Minnesota in a new study published in the Proceedings of the National Academy of Sciences.
Groundbreaking research from Tel Aviv University may lead to a significant breakthrough in the battle against deadly brain cancer.
Patients with glioblastoma receiving temozolomide in the morning had an average overall survival of about 17 months, compared to an average overall survival of approximately 13.5 months for those taking the drug in the evening.
Due to their ability to preserve healthy tissues and to provide an effective and long-lasting response, stem cells (SCs) with tropism for tumour cells have attracted considerable attention in the scientific community. As is the case here, SCs can be used to target brain tumour cancer cells, especially high-grade malignant gliomas like GB, by overcoming the resistance and exerting benefits for patients affected with such lethal disease. Herein, we will discuss the research knowledge regarding SC-based therapy for the treatment of GB, focalising our attention on SCs and SC-released extracellular vesicles modified to express/load different antitumour payloads, as well as on SCs exploited as a diagnostic tool. Advantages and unresolved issues of anticancer SC-based therapy will also be considered.
Survival with Optune + TMZ vs TMZ alone was significantly higher at the 2-year landmark analysis and remained higher at 5 years