"Glioblastoma takes its cues from hormones released by the same central clock in the host that establishes the body's regular daily rhythms," said Erik D. Herzog, PhD, the Viktor Hamburger Distinguished Professor and a professor of biology in Arts & Sciences, senior author of the study.

The team designed a unique trispecific antibody encoded in a DNA-encoded delivery mechanism. Their DNA-encoded trispecifics, named "DTriTEs," linked cancer-killing T cells through the CD3 protein with two different glioblastoma antigens: the IL-13Rα2 protein and the EGFRvIII protein. This allows the immune system's T cells to be alerted and activated when they encounter diverse glioblastoma tumors expressing either or both of these antigens.

Glioblastoma is one of the most aggressive and challenging forms of cancer, but with the right care, successful treatment is possible. The best hospitals for glioblastoma specialize in advanced neurosurgery, cutting-edge radiotherapy, and innovative therapies like electric field treatment and immunotherapy, offering the best chances for recovery.

Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location and invasive potential, with profound adverse effects for the patient if left to grow. Indeed, gross total resection may als be accompanied by unwelcome sequalae, underscoring the need for continued investigation. In the present work, we provide a scoping review of current CP management, with emphasis on our knowledge of their genesis, available treatment options, post-intervention clinical outcomes.

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. The standard of care involves maximal surgery followed by radiotherapy and concomitant chemotherapy with temozolomide (TMZ), in addition to adjuvant TMZ. However, the recurrence rate of GBM within 1–2 years post-diagnosis is still elevated and has been attributed to the accumulation of multiple factors including the heterogeneity of GBM, genomic instability, angiogenesis, and chronic tumor hypoxia. Tumor hypoxia activates downstream signaling pathways involved in the adaptation of GBM to the newly oxygen-deprived environment, thereby contributing to the resistance and recurrence phenomena, despite the multimodal therapeutic approach used to eradicate the tumor.

A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which is densely populated by protumoral glioma-associated microglia and macrophages (GAMs),” the researchers found. “Myeloid immune checkpoint therapy targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy is associated with toxicity and low bioavailability in solid tumors. In this work, we engineer a CAR T cell against epidermal growth factor receptor variant III (EGFRvIII), constitutively secreting a signal regulatory protein gamma-related protein (SGRP) with high affinity to CD47.

In a recent study published in Cancer Cell, Joyce, now at the University of Lausanne, revealed the findings from her team’s investigation into this question.2 The researchers discovered that fibrotic scar tissue formed after macrophage-targeted treatment acts as a safe harbor for dormant cancer cells and actively contributes to recurrence of resistant GBM. More importantly, they found that the process of scar formation—and therefore, tumor recurrence—can be stopped.

Recent trials have shown that immunotherapy can safely be delivered through injections into the cerebrospinal fluid. Scientists are now exploring how to adapt these methods to penetrate the tumor more effectively. Despite the promise of immunotherapy, making it effective for glioblastoma remains a challenge. Funding shortages have hampered brain cancer research in the past. But new initiatives are helping to recruit researchers from other fields to tackle glioblastoma.

Researchers at WashU Medicine have identified a possible way to make glioblastoma cells vulnerable to different types of immunotherapy. The strategy, which they demonstrated in cells in the lab, forces brain cancer cells to display targets for the immune system to attack. Glioblastoma is one of the most aggressive cancers, as illustrated by these brain scans from a patient with glioblastoma at initial diagnosis (left) and the same patient with a recurrent tumor (right).

Two main cell subtypes in glioblastoma drive tumor growth: developmental and injury-response. Specific genetic vulnerabilities (OLIG2, MEK, FAK, B1-Integrin) in these cells may be targeted to halt tumor recurrence. This is the largest CRISPR screen of glioblastoma stem cells, derived directly from patients.

The field of immunotherapy is evolving rapidly, with ongoing research expanding its potential applications across various diseases. Approved immunotherapy treatments are currently available for various cancers, like melanoma, breast and lung cancers. Immunotherapy can also be used to treat autoimmune conditions like multiple sclerosis and rheumatoid arthritis, infectious disease like HIV and hepatitis B and C, and in allergic disease.

This narrative highlights the complexity of the natural history of pediatric CP, its requirement for multidisciplinary management and the importance of “function sparing” therapies. Treatment algorithms experienced several changes over the last decades and will be subject to constant optimization. Implementation of experienced interdisciplinary networks generating individual therapeutic strategies is mandatory to avoid or minimize long-term consequences for the patient. Alternative treatments, including intracystic ORI combined with other therapies or even molecular genetic approaches may evolve further and offer more robust opportunities for function preservation in CP patients.

Pediatric craniopharyngioma is a rare, benign brain tumor that arises near the pituitary gland and hypothalamus, crucial areas for hormonal regulation and neurological function. Despite being non-cancerous, these tumors can cause significant health issues due to their location, leading to symptoms such as visual disturbances, hormonal imbalances, and cognitive challenges. Typically diagnosed in children aged 5 to 14, craniopharyngiomas require careful management to mitigate their impact on the developing brain and overall health.

Our experience advises that risk-adapted surgical strategies at diagnosis should aim for a maximal degree of resection, respecting the integrity of optical and hypothalamic structures to prevent severe sequelae and therein minimize consequences that could negatively impact the patient’s QoL. STR followed by PBT results in excellent disease control for pediatric CP, with a low risk of acute toxicity. Notably, PBT does not seem to worsen pre-existing complications, namely vision, the neurocognitive domain, and endocrine function, resulting in a safe and effective option for CP management.

Ultrasound-mediated drug delivery using micro/nanobubble technology holds great potential for revolutionizing the treatment of neurological diseases. Low-frequency ultrasound enables precise and safe delivery of therapeutic agents across the BBB, marking a key advancement in treating neurological disorders previously difficult to manage with conventional approaches. While essential clinical trials are underway, they represent just the initial phase of this groundbreaking technology. Advancing ultrasound-mediated drug delivery will require cross-disciplinary collaboration, optimized bubble technology, and strict adherence to FDA guidelines.

Our study exhibits an extensive investigation of the prognostic factors influencing survival outcomes in a cohort of patients diagnosed with IDH-wildtype glioma submitted to biopsy. This study highlights the importance of KPS both before and after surgery and any form of adjuvant treatment in determining patient outcomes. A decline in KPS post-operatively was indicative of poorer prognosis. We also clarified the adverse impact of cognitive impairment on PFS and OS for patients with mild cognitive deficits, and even higher for those severely impaired. Contrary to traditional fears regarding aggressive treatments in older patients, our data did not show a significant age-related impact on the three-month survival rate after adjuvant therapy in patients able to comply with treatment. While the volumetry, location, and hemisphere dominance of gliomas did not appear as significant predictors, lack of contrast uptake in imaging studies did, and it was associated with a notably poorer PFS and OS, as an independent variable. Finally, a critical observation from our data is the clear survival benefit associated with adjuvant therapies post-biopsy, irrespective of their pre-operative clinical status.

Scientists from the University of Geneva have developed CAR-T cells targeting the PTPRZ1 marker on glioblastoma cells, a promising step toward more effective treatments. These engineered immune cells showed the ability to attack both marked and unmarked tumor cells without harming healthy cells, successfully extending the lives of mice in preclinical trials.

Researchers have developed a promising CAR-T cell therapy targeting glioblastoma, the most aggressive brain tumor. The therapy uses genetically modified T cells to target a specific marker on tumor cells, potentially overcoming the limitations of traditional treatments. Notably, these CAR-T cells also show an ability to fight tumor cells lacking the marker, suggesting a bystander effect. Early trials in mice demonstrate that this approach effectively controls tumor growth with minimal toxicity, setting the stage for human clinical trials.

Researchers have discovered that the antidepressant vortioxetine effectively combats glioblastoma, a deadly brain tumor, in lab tests and in mice. This drug, already FDA-approved, crosses the blood-brain barrier and could potentially improve treatment for glioblastoma patients when combined with standard therapy.

In a first-in-human clinical trial, an mRNA-based cancer vaccine for glioblastoma showed promising results by inducing T-cell responses in over three-quarters of patients with an acceptable safety profile. The vaccine was able to generate new immune responses and break through immune tolerance to the tumor.