The establishment of a national Glioblastoma (GBM) Awareness Day has, in many ways, driven significant progress for the GBM and entire brain tumor community.
This year as we recognize the fifth annual Glioblastoma Awareness Day, it’s important that we take stock of these accomplishments, which have only been achievable through the dedicated advocacy and efforts of this community, while acknowledging we all have more we can and must do.
Five Advancements Since the Inaugural GBM Awareness Day
1. The U.S. government is taking encouraging action
While ultimately, no amount of investment is enough until we have cures and better quality of life, the U.S. government has heeded many of the original calls to action from the first Glioblastoma Awareness Day in 2019.
We’ve also seen steady increases in funding over the past several years for the National Institutes of Health (NIH) and the National Cancer Institute (NCI), and this has had particularly strong dividends for brain cancer and glioblastoma. The NIH records that it funded $360 million in brain cancer research in Fiscal Year 2019. For the upcoming Fiscal Year 2024, the agency is estimating it will spend $456 million on brain cancer*.
Finally, in 2021, the NCI, at the urging of Congress, made a strategic investment specifically in glioblastoma research with the launch of the Glioblastoma Therapeutics Network (GTN). The GTN is a highly experienced group of leading researchers from across the country to drive potential new therapies from pre-clinical development into pilot clinical studies in humans. While the program will benefit from increased and sustained funding, its formation was an encouraging sign that Congress and the Executive Branch were listening.
2. More accurate diagnoses and treatments are now possible
Just a few months after the first-ever Glioblastoma Awareness Day in 2019, the community got exciting news that a drug called Rozlytrek (entrectinib) was approved as a treatment for patients 12 years or older whose tumors have a specific genetic defect known as an “NTRK gene fusion.” While the drug wasn’t developed specifically for glioblastoma, the fact that its developers used a precision medicine approach (called a “tissue-agnostic” therapy) to target a specific mutation and not cancer-type, means that individuals with glioblastoma can use this drug if they are found to have the NTRK fusion. While only about 1% of patients diagnosed with GBM are estimated to have a tumor with an NTRK fusion, that equates to about 140 individuals every year who now have an additional treatment option to explore. Rozlytrek was preceded, in 2018, by another NTRK fusion drug called Vitrakvi (larotrectinib) that the same population of patients with GBM can also potentially benefit from.
Similarly, in 2022, the FDA approved the combination of two oral drugs called Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of advanced tumors that have a mutation called “BRAF V600E.” The approval includes use in both adult and pediatric (older than 6 years of age) high- and low-grade glioma patients with this mutation whose tumors progressed after prior treatment. Again, while the BRAF V600E mutation is only estimated to be prevalent in approximately 3% of glioblastomas, this means an estimated 420 patients and families dealing with a GBM diagnosis each year will have additional treatment options.
3. Biopharmaceutical companies are stepping into brain cancer research and development
Since late 2019, there have been a number of major business transactions in the brain cancer R&D ecosystem, with more larger companies than ever entering into partnerships or deals to license and develop investigational products from smaller biotechnology companies. This is a promising sign for GBM drug development overall. During this same time period, NBTS’s own affiliated venture philanthropy arm, the Brain Tumor Investment Fund, has launched and made six strategic investments in innovative companies trying to develop new products to benefit patients with brain tumors, including glioblastoma.
4. Innovative treatment modalities are beginning to reach patients
We are now seeing more novel approaches to treating glioblastoma move toward reality. Some of these strategies might have been considered just science fiction not long ago, but promising early data on these potential treatment methods are buoying hope that they soon might make real impacts for patients with glioblastoma.
Brain Tumor Investment Fund portfolio company Alpheus Medical is studying the use of a helmet-like device that uses “sonodynamic therapy” – or soundwaves from ultrasound technology – combined with a fluorescent drink to break up glioblastoma cells. Other research teams are attempting to use photodynamic therapy, or light, to treat GBM in similar fashion. Even more are exploring the use of focused ultrasound devices to help transport drugs into the brain to treat tumors like glioblastoma.
Finally, NBTS has launched a major consortium with a special focus on developing a treatment modality that targets glioblastoma and other tumors’ DNA Damage Response (DDR) network. The DDR is what allows cells, including cancer cells, to repair themselves after they’ve been damaged by things like chemotherapy and radiation. This presents the field with a great opportunity to find drugs that could effectively block a cancer cell’s ability to repair its broken DNA so that additional treatments can effectively kill the tumor. Our DNA Damage Response Consortium is rapidly testing different combinations of DDR-targeting treatments and preparing the most promising to enter clinical trials.
5. We’ve learned how to harness technology to improve access to care
While largely propelled by the COVID pandemic, the medical and policy community has begun to really embrace telemedicine as a way to make cancer care more accessible and even improve quality. Telemedicine has allowed patients with glioblastoma and all brain tumors to receive care at home, reducing travel and time burdens to care. Improvements in telemedicine appointments have enabled neurological assessments, while allowing discussions about imaging and treatment strategy to occur in ways that are less burdensome and cost prohibitive for many people. If brain tumor treatment is “work,” then telemedicine has enabled patients and their families to have better work-life balance.
Five Challenges We Still Must Overcome to Conquer and Cure GBM
While there has never been a more promising time in glioblastoma research, there are still significant hurdles that need to be overcome to reach our ultimate goal of delivering cures and more effective treatments to all patients with glioblastoma and brain tumors.
1. Getting anti-cancer drugs into the brain
The brain is protected from toxins and other potential dangers by a tightly-woven network of blood vessels called the “blood-brain barrier.” Unfortunately, the blood-brain barrier also prevents many of the drugs that are designed to attack tumors from getting into the brain, too.
The research field has continued to experiment with ways to get effective drugs past the blood-brain barrier and into cancer cells, while not harming healthy brain cells.
There are many ongoing efforts to design not only more effective and safe brain-penetrant drugs, but also delivery techniques that could get a potentially otherwise effective drug across the blood-brain barrier, including the focused-ultrasound technology mentioned above. The brain penetrance of different drugs under evaluation is also an acute focus of NBTS’s DNA Damage Response Consortium.
2. Figuring out how to make immunotherapies — which are transforming cancer treatment in other fields — work for glioblastoma
Glioblastoma are considered “cold” tumors, immunologically. This means there aren’t the same amount of active cells in the immune system of the environment surrounding glioblastoma tumors as there are in many other cancers. As such, efforts to use immunotherapies to unleash the body’s own immune response to detect and destroy, which have been transformative in the treatments of several other cancers, have yet to work in glioblastoma.
However, the research field in neuro-oncology is currently working on several strategies to turn glioblastoma tumors from “cold” to “hot” by bringing in more of the immune system’s toughest fighters to the tumor environment.
3. Identifying ways of preventing or detecting GBM early
Significant improvements in survival and mortality rates across many other cancer types have been driven in large part by better public health awareness campaigns to help prevent or detect cancer in its earliest states, when it is most treatable, via screening techniques like colonoscopies or pap smears. But no such early detection methods exist for glioblastoma and other brain tumors. And unlike smoking cessation efforts’ direct effect on lung cancer rates, there are no known prevention-style activities individuals can undertake to lower their risk of developing glioblastoma.
Future hope in this regard may center around a few different approaches, including (but not limited to):
The potential to refine “liquid biopsy” techniques to the point where blood or cerebrospinal fluid tests could be used routinely in the clinical setting and perhaps as an earlier and less-invasive means to identify a potential glioblastoma before waiting until MRIs and surgery are ordered following symptom onset.
The potential to use the NBTS-funded identification of “extrachromosomal DNA”, or ecDNA, as a biomarker of early disease. While findings are still preliminary, the eDyNAmic group – which was recently created and funded by a major Cancer Grand Challenges grant – has identified the potential for ecDNA to serve as an early warning of esophageal cancer. These findings would need to be validated, confirmed in glioblastoma, and refined for clinical application, but represent a recent, exciting development.
Using public health awareness campaigns to ensure brain tumor patients have accurate information at their fingertips upon diagnosis to quickly ensure they get the best possible care options. This would include ensuring all glioblastoma patients are aware of clinical trial options right at the point of diagnosis and that they understand the need for their tumor to undergo advanced biomarker testing to see if they could potentially benefit from a targeted therapy like the NTRK and BRAF treatments mentioned above.
4. The ability for patients to affordably access the specialized healthcare services needed to treat such a difficult disease
Currently, many public and private insurance providers offer so-called “narrow network” insurance plans that are cheaper, but that can ultimately make it more difficult for cancer patients to access top-tier hospitals such as those dubbed “NCI Designated Cancer Centers.” Today’s cancer patients, particularly those with aggressive cancers like glioblastoma, need highly specialized surgery, advanced diagnostics, and imaging, as well as rehabilitative, supportive, and palliative care. They require their treatment to be expertly planned, navigated, and in line with the latest science. In fact, the standard of care guidelines in the United States notes that cancer patients often receive their best care while in a clinical trial. NCI Designated Cancer Centers are at the forefront of developing and offering state-of-the-art therapies for cancer patients, including advanced diagnostics and the latest clinical trials.
NBTS is currently working to address the issue of narrow network health plans, as well as other issues impacting access to affordable and timely care, through support of measures like the “Stop The Wait Act.” And we need advocates’ voices to help ensure these policies work for patients and families.
5. Enrolling more patients in clinical trials
As noted above, the organization that sets the standards for treatment guidelines for cancer patients, the National Comprehensive Cancer Network, states that the best care for any patient with cancer, including glioblastoma, is on a clinical trial. Yet too few patients enroll on clinical trials, and many past studies (including surveys by NBTS) have identified various barriers to getting patients on trials, including a lack of awareness.
Clinical trial design has been slow to innovate, and many trials fail to effectively learn from every patient while minimizing the number of patients needed in so-called “control” or “placebo” groups. Trial design and recruitment efforts, combined with historical mistreatment, have also resulted in inequitable access to clinical trials for minority or underserved populations.
While significantly more work is needed on these issues, in recent years we have seen promising signs of progress, including formal guidance from the FDA to help ensure diversity and equity in clinical trial participation; the use of hybrid or decentralized trials to lower geographical barriers; the use of innovative designs like GBM AGILE to minimize the number of patients needed in control arms; and exploration into the feasibility of “external control arms” and real-world data collection to potentially reduce the need for control arms, while still maintaining data integrity from these studies. These all remain major topics for forums like NBTS’s Research Roundtable series.
Glioblastoma Awareness Day is an important time to remember our collective mission and that, working together, we can continue to build on this progress and overcome the challenges that face us on our way to future breakthroughs.