Glioblastoma Research in 2025: Overcoming the Blood-Brain Barrier and Advancing Drug Delivery

Glioblastoma (GBM) remains one of the most aggressive and devastating cancers today. Despite decades of research, median survival after diagnosis still ranges from 12 to 18 months.

With an incidence of more than 13,000 new cases annually in the US alone, this aggressive brain tumour has earned its reputation as a “lightning bolt killer.” It strikes without warning, carries no known genetic predisposition and is almost uniformly fatal. Shockingly, fewer than 7% of patients live to see five years post-diagnosis.

Unlike many other cancers, where advances in treatment have dramatically improved survival, GBM continues to challenge researchers and clinicians. As John Climaco, CEO of CNS Pharmaceuticals, explained in our interview, much of this difficulty comes down to the blood-brain barrier.

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The Blood Brain Barrier (BBB) Challenge

Why has progress slowed? Experts point to a major factor: the blood-brain barrier (BBB). While this carefully controlled network of endothelial cells is vital for shielding the brain from toxins, it also prevents most potentially effective cancer drugs from reaching their target.

This paradox means that treatments that can kill glioblastoma cells in a petri dish often fail in patients because they simply cannot access the tumour.

Climaco emphasized that the problem lies less in the tumor cells themselves and more in the “transport mechanisms, or lack thereof, that allow otherwise helpful modalities to reach the site of the tumor in the brain.”

The Dual Challenge of GBM

GBM’s challenges also go beyond the blood-brain barrier. The tumor itself grows in a manner that is both invasive and resilient.

Neurosurgeons often liken the tumor’s spread to a spider’s web infiltrating healthy brain tissue, making complete surgical removal nearly impossible. Even the smallest remnants can trigger rapid regrowth.

Compounding the problem, GBM cells respond poorly to insult, whether from surgery, radiation or chemotherapy, and frequently return more aggressive than before.

“Even the most skilled neurosurgeon is going to have a tremendous difficulty accessing and resecting all of that tumor,” Climaco noted, adding that aggressive regrowth makes the challenge even greater.

This complex biology underscores why survival rates remain so dismal. Today, standard-of-care treatments extend life for some patients; however, the five-year survival rate remains less than 7%. For a disease as aggressive as GBM, that shortfall is staggering in 2025.

Rethinking How Drugs Cross the BBB

Researchers are now exploring creative ways to bypass or overcome the BBB. One emerging method is targeted ultrasound, which can temporarily open the barrier and allow drugs to pass through. Other teams are experimenting with intranasal delivery systems to sidestep the barrier altogether.

“Glioblastoma’s challenges also go beyond the blood-brain barrier. The tumor itself grows in a manner that is both invasive and resilient.”

— John Climaco

Another promising approach is to design drugs that naturally penetrate the BBB. Compounds like lipophilic anthracyclines and taxanes are being re-engineered to cross into the brain and selectively target tumor cells.

Unlike novel therapies with uncertain mechanisms, these drugs are based on decades of proven success against other solid tumors.

The innovation lies not in how they kill cancer cells but in how they reach them. By modifying their structures, researchers have developed molecules that bypass active pumping mechanisms like multidrug resistance (MDR) and p-glycoprotein (PGP), arriving in the brain in high concentrations where they are most needed.

Climaco described this as a “back-to-basics strategy,” one that could finally deliver a reliable, one-size-fits-most option for patients.

Digital Health and Imaging: A New Lens on GBM

In addition to drug development, advanced imaging tools are transforming GBM research and care. Traditional MRI scans often confuse tumor growth with pseudo-progression, a treatment-related swelling that mimics recurrence. In the past, this misinterpretation could prematurely end a promising treatment for a patient with little time to spare.

With more sophisticated imaging, sometimes enhanced by AI-driven analysis, clinicians can now better distinguish between edema and actual tumor progression. This not only prevents patients from being removed from trials unnecessarily but also ensures they continue receiving therapies that might extend survival.

Climaco explained that this issue of pseudo-progression is common, and more advanced imaging gives physicians confidence to keep patients on potentially effective treatments longer.

The Power of Advocacy and Keeping GBM in Focus

Despite its rarity, glioblastoma resonates deeply in the public consciousness. That is partly because survival is so limited, with a median survival of just 14.6 months, and almost everyone knows a story of someone lost to the disease.

Unlike more common cancers, such as breast cancer, where survival rates have dramatically improved, GBM still carries a tragic finality.

Climaco emphasized the importance of advocacy, likening GBM to a “lightning bolt killer” with no precursors and no biomarkers, making it crucial for families and advocacy groups to keep the disease at the forefront of policymakers and the public.

Patient advocacy groups play a critical role in shaping research priorities and lobbying for funding. Their efforts help keep GBM visible to policymakers and research institutions at a time when budget cuts often force hard decisions. They also remind the world that while GBM is rare, its lessons could extend far beyond neuro-oncology.

Cracking the code of the BBB, for example, has implications not only for brain cancer but also for Alzheimer’s disease, Parkinson’s and other neurologic conditions.

Quality of Life and Rethinking Trial Endpoints

Traditionally, success in oncology trials has been measured by overall survival (OS). While this remains the gold standard, researchers are beginning to argue that quality of life should weigh equally in evaluating treatments.

“With more sophisticated imaging, sometimes enhanced by AI-driven analysis, clinicians can now better distinguish between edema and actual tumor progression.”

— John Climaco

For GBM patients, this question is exceptionally pressing. Climaco pointed out that future trial design must balance survival with quality of life: “We want people not just to live longer, but to live fuller lives.”

The new generation of BBB-penetrating drugs offers hope not just for survival but for better-tolerated therapies.

Early trials suggest that these drugs can be used safely over long periods without debilitating side effects such as cardiotoxicity, giving patients the chance to live their final months or years with dignity, energy and connection to loved ones.

What’s Next for GBM Research?

Looking forward, the field faces two pressing realities. First, some high-profile, experimental immunotherapies, though scientifically elegant, have yet to demonstrate durable survival benefits.

Second, their cost is staggering. Climaco noted that in some cases, companies have spent as much as $1 million to $3 million per patient to achieve only a few additional months of survival. He explained that such figures highlight the ethical and economic challenges of pursuing therapies that benefit very few while consuming extraordinary resources.

A shift is underway toward cost-effective, broadly applicable therapies. Climaco compared some of the high-profile scientific advances in neuro-oncology to “building the roof on the house before you build the foundation.” By refining tried-and-true chemotherapy backbones to penetrate the brain, his company is focused on building that foundation, therapies that can work for most patients, before reaching for the roof.

Glioblastoma remains a formidable adversary, but optimism is returning to a field once described as a “graveyard for drugs.”

Advances in BBB research, drug design, imaging and patient advocacy are converging to open new possibilities.

While GBM is rare, its impact is profound, and the fight against it will shape not just the future of neuro-oncology but also the treatment of many other brain diseases.

For now, patients and families continue to push researchers, clinicians and policymakers toward solutions that deliver not just longer lives but better ones. And in that push lies real hope for the future.