Glioblastoma

The dynamic TME is a key driver of cancer progression and presents pro-malignant biophysical signals including ECM composition, density, stiffness, and interstitial fluid flow, which helps direct the flow of soluble cues, increases the intertumoral pressure on the cells, and generates hypoxic regions. Ultimately, these factors work together to promote tumor growth and disease progression; however, these factors also dysregulate immune cells through the production of immunosuppressive cytokines, the recruitment of inhibitory immune cells, and/or the conversion into tumor-supportive tumor-associated immune cells. Biomedical research has made strides in elucidating the underlying mechanisms of the biophysical TME on immunosuppression through novel bioengineered tools and platforms.

Curcumin was able to reduce tumor growth in rodent xenograft models of glioma. This antiglioma effect of curcumin was observed for both orthotopic and heterotopic animal models and for different types of glioma cells, administration routes, and curcumin formulations. The effect of curcumin was higher for longer treatment durations. Although the presence of publication bias was identified, this does not invalidate curcumin’s effectiveness against glioma. The findings obtained with the present meta-analysis are encouraging and might foster future investigation on the potential therapeutic use of curcumin against such devastating diseases as glioma.

In a world-first, the new technique has been proven for glial tumors including glioblastoma (GBM), the most commonly-diagnosed type of high-grade brain tumor in adults.

This study provides novel insights into the dynamic interactions between patient‐derived GBM tumor cells and GAMs and sheds light on potential approaches to repolarize GAMs toward a more anti‐tumorigenic state. Using our models, GAM‐GBM interactions can be studied in a clinically relevant manner, while providing new opportunities to discover promising immunomodulatory targets.

The combination demonstrated encouraging results including a median survival of 14.5 months, median duration of response of 13.1 months, and median progression-free survival (PFS) of 5.5 months. The survival rate of 57.4% and 43.1% was observed at 12 months and 18 months respectively.

Strategies to overcome this immunoresistance include activation of the peritumoral inflammatory microenvironment; with a better understanding of the dynamics of the peritumoral microenvironment and improved preclinical tools, we can possibly develop more personalized and targeted treatments that could have a significant impact on patient survival [22]. The future direction of GBM therapy will include a combined approach that, in contrast to the inescapable current treatment modality of maximal resection followed by chemo- and radiotherapy, may combine a multifaceted immunotherapy treatment with the dual goals of directly killing tumor cells and activating the innate and adaptive immune response.

“This electrical activity propels rapid cancer cell proliferation, making it a hallmark of the disease,” Rawson explains. “Our insight was that by manipulating these underlying electrical pathways, we could potentially impede or even eliminate cancer cells. However, at that juncture, no suitable technology existed to precisely target these pathways and exert control over cell growth or the eradication of cancer cells.”

The intriguing case showcasing transient GBM regression after Bacillus Calmette–Guérin (BCG) therapy for bladder cancer prompts a critical need for a meticulous investigation into its underlying mechanisms and therapeutic prospects. While the precise mechanisms remain enigmatic, the potential systemic immunomodulatory effects of BCG on GBM warrant in-depth scrutiny. This scenario prompts pivotal inquiries into the complex interplay between systemic immune responses and the intricate microenvironment within GBM. An extensive exploration into the prospective immunomodulatory roles of BCG or analogous immunotherapies in GBM therapy holds significant promise.

Scientists at the Gladstone Institutes have published a paper in Cell Reports that describes a CRISPR-based technique for treating primary glioblastoma, a common and aggressive form of brain cancer. The paper, titled “Targeting the non-coding genome and temozolomide signature enables CRISPR-mediated glioma oncolysis,” describes the technique, which the researchers have called “genome shredding.”

After my diagnosis with glioblastoma, an aggressive and terminal type of brain cancer, knitting became a way to keep my hands busy and my mind calm. As I recovered from brain surgery and went through six weeks of daily radiation, I knit dozens of simple cotton dishcloths for my friends and family to thank them for their support. Each took only a few hours to make, but every stitch made me feel emotionally connected to those who cared for me.

We can safely state that oncolytic viral therapy is a well-established cancer treatment modality at this point. The efficacy of oncolytic virus therapy is anticipated to increase when coupled with immunotherapy since the common feature that plays a significant role in showing anticancer effects during oncolytic activities is the formation of specific antitumor immunity. Functional transgenes would enable oncolytic viruses to be equipped with a wide range of anticancer capabilities in the future. Based on the kind and stage of cancer, a combination of suitable viruses may then be selected from this panel. Oncolytic viral therapy appears to be the beginning of a new age in cancer treatment, where patients have the freedom to choose this treatment option.

Using standard bioinformatics and newer AI-based approaches, Datta’s TIME Lab began analyzing different genes expressed in the tumor microenvironment related to the extracellular matrix — or the scaffolding cells create to support future cell adhesion, migration, proliferation and differentiation — and other various cell types. What they found was a surprising, fairly new cell type: perivascular fibroblasts. These fibroblasts are typically found in the blood vessels of a healthy brain and deposit collagen to maintain the structural integrity and functionality of brain vessels.

Glioblastoma is an extremely aggressive type of brain cancer and is the most common type of primary malignant brain tumor in adults. There is currently no cure for it and, due to its fast-growing nature and location, it is very difficult to treat. But could CAR-T cell therapy – which has been so groundbreaking in treating blood cancers – be the best hope for successfully treating, and perhaps even curing, glioblastoma?

A largely understudied cell could offer new insight into how glioblastoma, an aggressive, primary brain cancer is able to resist immunotherapy, new research shows.

CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) is a biopharmaceutical company focused on developing innovative therapies for central nervous system disorders, specifically aggressive brain cancers. One of their leading treatment candidates is Berubicin, a chemotherapy drug that interferes with the DNA of cancer cells to inhibit their growth and potentially shrink tumors. Unlike traditional chemotherapy drugs, Berubicin has the ability to penetrate the blood-brain barrier and directly target cancer cells in the brain, increasing its potential effectiveness.

In summary, we show that Hsp70 in the circulation and on the membrane of tumor cells, in the presence of IL-2, stimulates NK cells in patients with grade 3 glioma and possibly confers a survival benefit to these patients, whereas in patients with grade 4 GBM with low CD4+ helper T cells, the NK cell stimulation is hindered. However, in the latter patients, circulating levels of Hsp70 are significantly elevated from the onset of the tumor disease and may serve as a diagnostic and prognostic tumor marker.

Our data suggests that postoperative intracranial hemorrhage is not caused by prophylactic anti-coagulation but rather is a surgical complication or the result of antithrombotic therapy. However, thromboembolic events worsen patient outcomes far more than postoperative bleeding. The fact that bleeding may occur as a complication of life-saving lysis therapy in the setting of a thromboembolic event should be included in this cost–benefit consideration.

Recent studies and technological developments have advanced our understanding of the complex and intricate interactions between glioblastoma and the tumour microenvironment, providing insights into how glioblastoma evades current treatments and paving the way towards more effective therapies in the future.

This study auditing the radiological volume parameters obtained from basic MRI sequences, specifically, the ratio of the initial T2 volume abnormality to the T1gad volume, provides information on treatment prognosis and pattern of relapse in glioblastoma.

The intriguing case showcasing transient GBM regression after Bacillus Calmette–Guérin (BCG) therapy for bladder cancer prompts a critical need for a meticulous investigation into its underlying mechanisms and therapeutic prospects. While the precise mechanisms remain enigmatic, the potential systemic immunomodulatory effects of BCG on GBM warrant in-depth scrutiny. This scenario prompts pivotal inquiries into the complex interplay between systemic immune responses and the intricate microenvironment within GBM. An extensive exploration into the prospective immunomodulatory roles of BCG or analogous immunotherapies in GBM therapy holds significant promise.

Using a novel technique they've dubbed "cancer shredding," the researchers programmed CRISPR to zero-in on repeating DNA sequences present only in recurrent tumor cells-;and then obliterate those cells by snipping away at them. Working with cell lines from a patient whose glioblastoma returned after prior treatments, the team used CRISPR to destroy the tumor cells while sparing healthy cells.

CAR T-cell immunotherapy stands as a transformative approach in cancer treatment, offering promising potential for GBM therapy. While immunotherapy for GBM is still in its early stages, recent progress in neuroimmunology and cancer immunotherapy has sparked optimism about its therapeutic possibilities. Insights acquired from preclinical and clinical studies on CAR T cells serve as the basis for future trial designs. Early trial outcomes highlight such challenges as the suppressive tumor microenvironment and tumor heterogeneity, emphasizing the need to address these hurdles for improved CAR T-cell therapy efficacy. Targeted experiments have yielded promising therapeutic results, offering potential solutions to overcome treatment obstacles.

Glioblastomas arise from glial cells in the brain and are subcategorized as astrocytomas, brain stem gliomas, ependymomas, mixed gliomas, oligodendrogliomas, and optic pathway gliomas.1 There are 4 grades of glioma based on the tumor’s growth potential and aggressiveness. Glioblastoma multiforme (GBM), also referred to as grade 4 astrocytoma, is an aggressive brain tumor with a grave prognosis. The disease accounts for 45.2% of all malignant central nervous system (CNS) tumors, 80% of all primary malignant CNS tumors, and 54.4% of all malignant gliomas, making it the most common type of malignant brain tumor.2

There is currently a high unmet need for effective treatments for glioblastoma. While there are some therapies available, such as surgery, chemotherapy and radiation, they do not appear to be very effective in prolonging survival. In recent years, there has been a growing interest in immunotherapy and precision medicine, with researchers working to develop treatments that can more effectively target the specific genetic mutations and molecular pathways involved in glioblastoma growth. However, success in these efforts has been limited.