Glioblastoma (or GBM) is the most common and most aggressive malignant brain tumor — or brain cancer. It is also one of the most complex, deadly, and treatment-resistant tumors of any cancer.
Despite first being identified in the scientific literature in the 1920’s, there have only been four drugs and one device ever approved by the FDA for the treatment of glioblastoma. None of these treatments have succeeded in significantly extending patient lives beyond a few extra months.
In addition to being life-threatening, GBM — and its harsh treatments — inflict devastating upon the body’s fragile command center, the brain, which controls cognition, mood, behavior, and every function of every organ and body part. Many patients will those their ability to work, drive, and a host of other functions that contribute to one’s sense of self and independence.
Glioblastoma is also one of the more expensive cancers to treat, often leaving patients and families with major financial hardship on top of the burdens of the disease.
Yet, science is advancing rapidly and there are promising research strategies moving forward.
Glioblastoma has been especially difficult to treat for a few reasons, including (but not limited to):
- Glioblastoma cells do not stick together in a solid ball that can be easily removed, as one might imagine. Instead, GBM cells tend to spread out (diffuse) from a main tumor mass like tentacles. This makes full surgical removal virtually impossible — inevitably some cells get left behind. This is often exacerbated by the location of these tumors amidst delicate — and vital — brain tissue, which pains must be taken to not damage.
- Unfortunately, the cancerous cells left behind after surgery are also very heterogeneous — meaning they are not all identical in their genetic and molecular makeup, even within the same patient’s tumor. In fact, glioblastomas can often be made-up of many different unique cell types that each harbor distinct sets of mutations and alterations. This makes identifying a single therapy that can kill all the different cell types particularly trying.
- Further, GBM cells have proven to be particularly adaptable. Even when treatment targets have been identified in the past, these tumors have proven adept at avoiding, or escaping, the effects of the treatment, by either developing resistance or simply using a new biological mechanism to continue to grow.
- Compounding these challenges is what is known as the “blood-brain barrier.” The blood-brain barrier exists to protect the brain from harmful chemicals, pathogens, or toxins, but that also means that most drugs (which are typically chemical structures) can’t enter the brain, either, to treat the tumor. This means the ‘menu’ of potential drugs researchers can select from to test against GBM is significantly limited compared to most cancers.
- Finally, because GBM has proven a very difficult area to create and develop drugs for — and it has a relatively small patient population compared to other cancers — many biopharmaceutical companies are reluctant to invest significant resources in this disease area for fear of failure or small returns.
Working Toward Solutions
Because of its dire prognosis and the urgent unmet medical need, GBM has always been a major focus of NBTS’s research funding portfolio. That focus was accelerated when NBTS took the ambitious step of launching the Defeat GBM Research Collaborative in 2013 — our boldest, most concerted initiative ever to discover the ‘Achilles Heels’ of these tumors and develop medicines which could exploit these vulnerabilities.
From this five-year program investment alone, we’ve identified:
- That the cells that make up a GBM tumor have a unique metabolism, and compared to healthy cells become overly-reliant (or addicted) to certain nutrients to fuel their aggressive growth. Defeat GBM-funded researchers have identified a number of tricks these tumors play to gobble up these nutrients, and how blocking the tumor from using these tactics could a promising new treatment approach. Read more.
- How tiny, circular fragments of DNA (called extrachromosomal DNA, or ecDNA) that contain cancer-driving mutations can “jump” off chromosomes (where genes and DNA are usually stored) and subsequently make glioblastoma tumors much more complex and difficult to treat. If researchers can now figure out how these tiny fragment jump off the chromosomes, and prevent them from doing so in the first place, it could make glioblastoma significantly easier to treat. Read more.
- That an altered cellular protein called “PTEN” plays a critical role in reversing the effects of radiation treatment in GBM cells. Importantly, the team found a type of drug that may be able to stop the actions of the altered PTEN and make radiation treatment more effective for glioblastoma patients. Read more.
- That a simple change in the sequence and timing of immunotherapy drugs may significantly improve the survival of GBM patients. Read more.
- That pieces of DNA (called circulating-tumor DNA, or ctDNA) from glioblastoma cells are shed into patients’ cerebrospinal fluid (CSF), and that doctors can take a sample of CSF during routine lumbar punctures in the clinic (spinal tap) and extract and test these pieces of ctDNA to see what mutations are present in a patient’s tumor. This could allow doctors to monitor a patient’s tumor during treatment in a less invasive manner and see how the tumor evolves and responds (or doesn’t) to certain treatments. Read more.
NBTS is seeking to take these, and other emerging and promising treatment strategies, and evaluate them in early-phase clinical trials.
Finally, NBTS is supporting a major, game-changing new clinical trial called GBM AGILE that completely re-imagines how treatments are evaluated in mid-stage clinical trials. GBM AGILE, an adaptive platform trial, will ultimately test multiple new potential treatments simultaneously (instead of one at a time) and lower the cost, shorten the time, and decrease the amount of trial participants needed to advance an investigational drug toward approval and the market.
Give today for GBM Awareness Day
On GBM Awareness Day, we honor the patients, families, and care partners who have faced glioblastoma — the most common, complex, treatment-resistant, and deadliest type of brain cancer. There is no question that the urgent and unmet needs of the GBM community continue to grow.
With such limited progress made in treating these aggressive and complex tumors, we know that the time to act is now. Make a gift today, and help to accelerate the rate at which we discover, develop, test, and approve new treatments, while working together to advance a cure.