Glioblastoma (GBM) is a name that often evokes fear and uncertainty, and for good reason. As the most common and aggressive form of primary brain cancer, it strikes without discrimination, affecting people of all ages, backgrounds, and walks of life. Despite decades of research and advancements in medical technology, glioblastoma remains a formidable challenge, with a prognosis that has seen little improvement over time. In this post, we’ll explore what glioblastoma is, its impact on patients, current treatment approaches, and the promising research that offers hope for the future.
What Is Glioblastoma?
Glioblastoma, also known as glioblastoma multiforme, is a type of glioma—a tumor that originates from the glial cells in the brain, which support and protect neurons. It accounts for about 14.5% of all central nervous system tumors and 48.6% of malignant brain tumors, making it the most prevalent and deadly primary brain cancer. The tumor is classified as a grade IV malignancy by the World Health Organization (WHO), indicating its highly aggressive nature. Glioblastomas are characterized by rapid growth, infiltration into surrounding brain tissue, and a complex, heterogeneous cellular makeup that makes them resistant to treatment.
One of the defining features of glioblastoma is its molecular diversity. The WHO classifies glioblastomas into three main categories: IDH-wildtype (about 90% of cases, often called primary glioblastoma, typically affecting older adults), IDH-mutant (about 10%, known as secondary glioblastoma, often arising from lower-grade gliomas in younger patients), and glioblastoma NOS (not otherwise specified, when IDH status cannot be determined). These molecular distinctions are critical because they influence prognosis and treatment response. For instance, IDH-mutant glioblastomas tend to have a slightly better prognosis, with a more protracted course, while IDH-wildtype tumors are more aggressive.
The Grim Reality: Prognosis and Challenges
The statistics surrounding glioblastoma are sobering. The median survival for patients is approximately 15 months, even with the best available treatments. The five-year survival rate is a mere 6.9%, and fewer than 1–3% of patients survive beyond five years. Survival rates have remained largely unchanged for decades, a stark contrast to the progress seen in other cancers like breast or leukemia. Glioblastoma’s lethality stems from several factors:
- Invasiveness: The tumor’s tentacle-like extensions invade healthy brain tissue, making complete surgical removal nearly impossible without damaging critical brain functions like speech or movement.
- Resistance to Treatment: Glioblastoma cells, particularly cancer stem cells, exhibit resistance to radiation and chemotherapy, often leading to recurrence. These stem cells share properties with neural progenitor cells, expressing markers like CD133 and CD44, which contribute to their resilience.
- Blood-Brain Barrier (BBB): The BBB, a protective barrier in the brain, prevents many drugs from reaching the tumor, limiting the effectiveness of systemic therapies.
- Immunosuppressive Environment: Glioblastomas create an environment that suppresses the immune system, making it difficult for the body to fight the tumor naturally.
The disease also takes a profound toll on patients’ quality of life. Because the brain controls cognition, mood, and bodily functions, glioblastoma and its treatments can lead to devastating symptoms, including memory loss, personality changes, seizures, and motor deficits. For many, the diagnosis feels like a death sentence, but as we’ll explore, there are glimmers of hope on the horizon.
Current Treatments: A Multimodal Approach
The standard treatment for glioblastoma has remained largely unchanged since the early 2000s, following a landmark clinical trial that established the current protocol. Treatment typically involves a combination of surgery, radiation, and chemotherapy, often referred to as the Stupp protocol:
- Surgery: The first step is maximal safe resection, where surgeons remove as much of the tumor as possible without harming critical brain areas. Tools like 5-aminolevulinic acid, which causes tumor cells to fluoresce under blue light, have improved resection rates (65% complete resection compared to 36% with conventional methods), but they haven’t translated into significant survival benefits.
- Radiation Therapy: Post-surgery, patients undergo 6 weeks of radiation, often combined with the chemotherapy drug temozolomide (TMZ). Radiation targets residual tumor cells, but its effectiveness is limited by the tumor’s diffuse nature.
- Chemotherapy: Temozolomide, an alkylating agent, is the cornerstone of chemotherapy for glioblastoma. A 2005 trial showed that adding TMZ to radiation extended median survival from 12.1 months to 14.6 months. However, TMZ is most effective in patients with a methylated MGMT promoter, a genetic marker that reduces DNA repair activity in tumor cells, making them more susceptible to the drug. For those with unmethylated MGMT, TMZ offers little benefit.
Beyond the Stupp protocol, other treatments are sometimes used, particularly for recurrent glioblastoma. Bevacizumab, an antiangiogenic drug, can control symptoms by reducing blood vessel growth in the tumor, but it doesn’t improve overall survival. Tumor-treating fields (TTFields), a device approved by the FDA in 2011 (under the name Optune), uses alternating electric fields to disrupt cancer cell division. While it has shown some promise as an adjuvant therapy, its acceptance remains limited due to mixed results and practical challenges.
The Human Cost: A Personal Story
To understand the impact of glioblastoma, consider the story of Juan Morales, a long-time parishioner at St. Martin of Tours and St. Dominic in the Bronx, who passed away from glioblastoma on March 25, 2025. Juan, a 68-year-old father and grandfather, was diagnosed in September 2023. Despite undergoing surgery, radiation, and chemotherapy, the cancer progressed rapidly, and he passed away 18 months after his diagnosis—a timeline consistent with the median survival for glioblastoma. Juan’s story, shared in a previous blog post, highlights the disease’s devastating effects, but also his resilience. Even as his health declined, he remained active in his parish, finding solace in his faith and devotion to Our Lady of Divine Mercy. His story is a reminder of the urgent need for better treatments.
Emerging Research: Hope on the Horizon
While glioblastoma remains a formidable foe, recent research offers hope. Scientists and clinicians are exploring innovative approaches to tackle the disease’s challenges, from immunotherapy to targeted therapies. Here are some promising developments:
- CAR-T Cell Therapy: In March 2024, researchers at Mass General Cancer Center reported dramatic results from a phase 1 trial of a new CAR-T therapy for recurrent glioblastoma. The approach, called CARv3-TEAM-E, targets two proteins on glioblastoma cells: EGFRvIII and wild-type EGFR. In the first three patients, tumors shrank significantly within days, though the response wasn’t sustained. The team is now working on strategies to extend the durability of the response, such as combining CAR-T with chemotherapy.
- Proton Beam Therapy: A January 2025 study from the Mayo Clinic showed that short-course hypofractionated proton beam therapy, combined with advanced imaging, improved overall survival in patients over 65 with grade 4 glioblastoma. The median survival was 13.1 months, compared to 6–9 months in prior studies, with some patients with favorable genetics surviving up to 22 months.
- Oncolytic Viruses and Immunotherapy: A 2023 clinical trial led by the University of Toronto and University Health Network tested a combination of an oncolytic virus and immune checkpoint inhibitors for recurrent glioblastoma. The therapy, which uses the virus to stimulate an immune response and the inhibitor to prevent the tumor from evading the immune system, extended median survival to 12.5 months—significantly longer than the typical 6–8 months.
- Targeting Tumor-Neuron Interactions: A 2023 study from the University of California, San Francisco, revealed that glioblastomas can hijack neuroplasticity—the brain’s ability to form new synapses—to fuel their growth. The protein TSP-1 was identified as a key mediator of this process. In mouse models, the drug gabapentin, which blocks TSP-1, slowed tumor growth, and a clinical trial is now planned to test this approach in humans.
- Precision Medicine: The drug vorasidenib, approved by the FDA in August 2024, targets IDH1 and IDH2 mutations in low-grade gliomas, which can progress to glioblastoma. In clinical trials, vorasidenib more than doubled progression-free survival, offering a new option for patients with these mutations. Researchers at Duke University, who played a key role in its development, are now studying its use in higher-grade tumors.
The Road Ahead: Challenges and Opportunities
Despite these advances, significant hurdles remain. Only about 11% of newly diagnosed glioblastoma patients enroll in clinical trials, often due to lack of awareness, physical or cognitive limitations, or the need to travel to academic centers. The tumor’s heterogeneity—both within a single tumor and across patients—makes it difficult to develop one-size-fits-all treatments. Additionally, the blood-brain barrier continues to limit drug delivery, though new approaches like nanocarriers and convection-enhanced delivery are being explored.
The lack of progress in glioblastoma treatment also raises questions about the current research paradigm. While genomic profiling has deepened our understanding of the disease, it hasn’t yet translated into meaningful survival gains. Some argue that the focus on molecular targets like EGFR, which is overexpressed in many glioblastomas, has been disappointing—multiple trials targeting EGFR have failed. This suggests that a broader, more holistic approach, perhaps combining therapies that target the tumor microenvironment, immune system, and tumor-neuron interactions, may be necessary.
Conclusion: A Call to Action
Glioblastoma remains one of the most challenging cancers to treat, but the recent wave of research offers hope that we may be on the cusp of breakthroughs. For patients and families, the disease is a harsh reality, but stories like Juan Morales’ remind us of the resilience of the human spirit. As a community, we can support the fight against glioblastoma by raising awareness, advocating for increased research funding, and encouraging participation in clinical trials. Organizations like the National Brain Tumor Society, which spearheads Glioblastoma Awareness Day each July, are leading the charge to drive progress.
For those affected by glioblastoma, every day is a battle, but it’s a battle they don’t have to fight alone. By continuing to push the boundaries of science and medicine, we can honor the memory of those we’ve lost and offer hope to those still fighting.
Sources:
- National Brain Tumor Society: Information on glioblastoma statistics and awareness initiatives.
- Mayo Clinic Comprehensive Cancer Center Blog: Details on proton beam therapy study (January 2025).
- Mass General Cancer Center: CAR-T therapy trial results (March 2024).
- University of Toronto and University Health Network: Oncolytic virus and immunotherapy trial (May 2023).
- University of California, San Francisco: Study on glioblastoma and neuroplasticity (June 2023).
- Duke Department of Neurosurgery: Information on vorasidenib approval and development (August 2024).
- Various scientific reviews on glioblastoma epidemiology, treatment, and molecular characteristics.