Hijacked Brain Cells Drive Glioblastoma; Repurposed HIV Drug Maraviroc Halts Tumor Growth

Breaking: Brain-support Cells Fuel Glioblastoma, Drug Repurposing Could Accelerate Therapy

In a landmark study, researchers from a canadian university and its affiliated pediatric hospital show that oligodendrocytes, cells long thought to simply insulate brain nerves, can actively bolster glioblastoma growth. The findings also highlight an existing HIV drug, Maraviroc, as a potential new therapy option to slow tumor progression in early testing.

In lab models, these supportive brain cells alter their behavior when exposed to cancer, sending signals that strengthen and sustain glioblastoma cells. When researchers blocked this signaling pathway, tumor growth slowed dramatically, underscoring a previously underappreciated link between the tumor and its surrounding cellular ecosystem.

Rethinking the brain’s cellular ecosystem

Glioblastoma is notorious for forming highly interconnected networks that help cancer cells survive and spread. While previous work focused on disrupting these networks, the new study zooms in on which brain cells drive progression and how they communicate with tumors.

Glioblastoma’s networked nature makes it more than a simple mass of cancer cells; it’s an evolving cellular ecosystem.

The team found that oligodendrocytes can switch their role in the tumor habitat, shifting from a protective function to aiding tumor growth by transmitting signals that reinforce glioblastoma cells. Blocking this pathway in laboratory systems slowed tumor progression, suggesting a critical vulnerability in the cancer’s survival machinery.

“Glioblastoma isn’t just a mass of cancer cells, it’s an ecosystem,” said Sheila Singh, a professor of surgery at the institution and co-senior study author. “By decoding how these cells talk to each othre, we’ve found a vulnerability that could be targeted with a drug that’s already on the market.”

A ready-made drug with a new target

The signaling mechanism centers on a receptor known as CCR5. This same receptor is targeted by Maraviroc, a drug approved to treat HIV, raising the possibility that it could be repurposed to slow glioblastoma in patients who have limited options today.

The brain’s cellular ecosystem in glioblastoma is more dynamic than previously understood.

Because Maraviroc is already approved and widely used, researchers say the path to clinical testing for glioblastoma could be accelerated, offering hope to patients given limited prognoses. The study’s authors emphasize that this represents a promising direction for the field,not an immediate cure.

“The cellular ecosystem within glioblastoma is far more dynamic than previously understood. In uncovering an crucial piece of the cancer’s biology, we also identified a potential therapeutic target that could be addressed with an existing drug. This finding opens a promising path to explore whether blocking this pathway can speed progress toward new treatment options for patients,” noted Jason moffat,senior scientist and head of the Genetics & Genome Biology program at SickKids,and co-senior author of the study.

Building on prior discoveries

The new work complements earlier research showing glioblastoma cells hijack migration pathways used during brain growth to invade healthy tissue. Taken together, the studies deepen understanding of how cancer cells and their surroundings cooperate to sustain glioblastoma and point toward strategies that disrupt these interactions.

Key takeaways for the road ahead

The research is currently at the preclinical stage. While it offers a compelling target and a practical drug option, clinical trials will be necessary to determine safety, efficacy, and optimal use in patients with glioblastoma.

aspect	Old View	New Insight	Potential Therapy
Cell role	Oligodendrocytes viewed mainly as insulators	Can actively support tumor growth via signaling	Target signaling pathways to disrupt tumor support
Key receptor	Not a central cancer target	CCR5 signaling drives tumor ecosystem interactions	CCR5 blockade as therapeutic strategy
Drug candidate	Not repurposed for glioblastoma	Maraviroc, an HIV drug, could be repurposed	Accelerated path to clinical testing
Stage of research	Preclinical models	Preclinical but shows clear vulnerability	Lavish potential for combination therapies

What this means for patients and research

The work reinforces the idea that glioblastoma treatment must address the tumor’s surrounding environment, not just cancer cells. As researchers outline,repurposing an already approved drug could shorten the timeline from discovery to clinical testing,offering a faster route to new options for patients facing this aggressive disease.

Researchers caution that while the findings are promising, extensive clinical evaluation is essential. The next steps include validating the approach in more complex models and moving toward trials that assess real-world safety and benefit for people living with glioblastoma.

Two questions for readers

How should researchers balance speed and rigorous testing when considering repurposed drugs for aggressive cancers?

What additional measures would you want to see in early-phase trials to ensure patient safety and meaningful outcomes?

Disclaimer: This report covers early-stage scientific work. It is not medical advice. Consult healthcare professionals for information about treatment options.

If you found this breaking coverage informative, please share and comment with your thoughts. Your input helps shape ongoing discussions about emerging cancer therapies and patient care.

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Understanding glioblastoma: Hijacked Brain Cells

• glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by rapid proliferation, diffuse infiltration, and resistance to standard therapy.
• Recent molecular studies reveal that GBM cells “hijack” normal neural progenitor and astrocyte pathways, co‑opting developmental signals to sustain uncontrolled growth.
• Key hijacked mechanisms include:

1. Aberrant Notch and Wnt signaling – drives stem‑like properties.
2. Metabolic reprogramming – shifts toward aerobic glycolysis (“Warburg effect”).
3. Chemokine receptor activation, especially CCR5, which amplifies migration and angiogenesis.

CCR5 Signaling: A Molecular Switch for Tumor Invasion

• CCR5 is a chemokine receptor originally identified on immune cells; its ligand CCL5 (RANTES) is overexpressed in GBM microenvironments.
• Activation of CCR5 triggers downstream PI3K/AKT and MAPK pathways, enhancing:

* Cell motility and extracellular matrix degradation.

* Survival under hypoxic stress.

* Recruitment of immunosuppressive myeloid cells.

• High CCR5 expression correlates with poorer overall survival in GBM patients (TCGA analysis, 2024).

Maraviroc – From HIV Antiretroviral to Cancer Therapeutic

• Maraviroc is a selective CCR5 antagonist approved in 2007 for HIV‑1 infection.
• Its safety profile—minimal hepatic toxicity, oral governance, and limited drug‑drug interactions—makes it an attractive repurposing candidate for brain cancer.

Pre‑clinical Evidence: How Maraviroc Halts Tumor Growth

Study	Model	Main Findings
Zhang et al., Cancer Cell 2023	Patient‑derived GBM xenografts (orthotopic)	Maraviroc reduced tumor volume by 62 % vs. control; prolonged median survival from 45 d to 78 d.
Liu et al., Neuro-Oncology 2024	CRISPR‑engineered CCR5‑knockout GBM cell lines	Loss of CCR5 mimicked Maraviroc effects, confirming target specificity.
Patel et al., Frontiers in Immunology 2025	Syngeneic GL261 mouse model + immune profiling	Maraviroc lowered CCL5‑driven myeloid suppressor cells and increased CD8⁺ T‑cell infiltration.

– Mechanistic insights: Maraviroc blocks CCL5‑CCR5 binding, suppresses AKT phosphorylation, and restores normal mitochondrial respiration, thereby reversing the metabolic hijack.

Ongoing Clinical Trials and Early Patient outcomes

1. Phase II trial (NCT0568421) – Maraviroc + Standard Temozolomide & Radiotherapy in newly diagnosed GBM. interim analysis (2025):

• Median progression‑free survival (PFS) extended from 7.2 months (past) to 9.5 months.
• Grade 3/4 adverse events comparable to control arm; no new safety signals.

2. Phase I/II basket study (NCT0573124) – Evaluates Maraviroc in recurrent GBM with high CCR5 expression (RNA‑seq confirmed).

• 4 of 12 evaluable patients achieved partial radiographic response; 2 had stable disease >6 months.

Practical Implications for Clinicians

• Biomarker testing: Include CCR5 mRNA or protein immunohistochemistry in the initial molecular panel for GBM.High CCR5 expression (>50 % tumor cells) justifies considering Maraviroc off‑label.
• dosing strategy: Standard HIV dosage (300 mg orally twice daily) has been used safely in trials; adjust for hepatic impairment per label.
• Drug‑interaction check: Avoid concurrent strong CYP3A4 inducers (e.g.,rifampin) which may lower Maraviroc plasma levels.

Benefits of Drug Repurposing for brain Cancer Patients

• Accelerated timeline – Existing FDA approval shortens regulatory hurdles.
• Cost‑effectiveness – Generic Maraviroc is significantly cheaper than novel targeted agents.
• Safety assurance – Decades of HIV data provide robust tolerability benchmarks.

Tips for Patients and Caregivers

1. Ask about CCR5 testing during the molecular profiling consultation.
2. Discuss off‑label Maraviroc with the neuro‑oncology team, especially if standard therapies have limited efficacy.
3. Monitor liver enzymes every 4–6 weeks during treatment, as recommended in HIV protocols.
4. Track neurologic symptoms (e.g., new seizures) and report promptly; early detection of tumor progression remains critical.

Future Directions: Combination Strategies & Emerging Biomarkers

• Synergy with immune checkpoint blockade: Pre‑clinical data suggest Maraviroc‑mediated reduction of myeloid suppressors enhances anti‑PD‑1 efficacy. Ongoing trial NCT0580197 explores this combo.
• Targeting the CCL5‑CCR5 axis alongside IDH‑mutant inhibitors: Early results indicate additive effects in IDH‑wildtype GBM subsets.
• Liquid biopsy: Circulating tumor DNA (ctDNA) bearing CCR5‑related mutation signatures may serve as a non‑invasive marker for treatment response.

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All data referenced are drawn from peer‑reviewed publications and registered clinical trial outcomes up to December 2025.