As local drug delivery technology evolves, the field is poised for monumental change.
Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor mainly found in adults. Even with the latest advances in cancer therapies, the few drugs that have crossed the blood-brain barrier (BBB) and reached the tumor directly face the hurdle of the BBB being disrupted in the process. With only about 5% of patients living 5 years after diagnosis, professionals urgently need a solution.
With advances in understanding what is needed to treat GBM, treatment approaches have begun to change. Scientists have traditionally focused on developing new drugs to target malignant tumors. However, drug development can take decades, and as the diagnosis of this disease continues, time is not on the side of oncology professionals. To quickly address this dilemma, scientists are turning to advanced methods of topical drug delivery and finding new ways to deliver therapies effectively while bypassing the BBB. With this paradigm shift from incorporating local drug delivery technology into GBM treatment, the field of oncology is poised for monumental change.
Paradigm shift to local drug administration
The primary thrust in cancer research and treatment has evolved towards a more personalized approach to treating tumors through precision medicine and therapy. We are entering a “genomic era” where scientists look at genomic patterns in each tumor to tailor drugs for optimal results.
Effective drug delivery remains one of the greatest challenges, despite recent advances in cancer care. Intravenous (IV) administration is not completely effective for GBM treatment because many drugs are still unable to enter the BBB, limiting efficacy. Despite this, the IV method of administration is still used with drugs that can better localize in tumors based on pharmacokinetic data. The potential to deliver much higher levels of drug directly to the tumor site with sustained release over a period of approximately 3 weeks, while maintaining minimal systemic drug exposure, represents a major shift in what is possible, not just in treatment. of GBM, but more generally in neuro-oncology.
Researchers looking to address this delivery dilemma have come to realize that packaging a drug with a formulation that can be delivered directly to the site of the brain tumor allows bypassing the BBB. Drug delivery using this packaging formulation can better encapsulate the drug and allow us to protect it from the degradation that occurs with IV administration, allowing for sustained delivery.
As new formulas are clinically explored to enable such extended release, the potential for improved overall survival and clinical outcomes for patients with GBM becomes more real. These clinical trials have the potential to enable local drug delivery of chemotherapy directly to brain tumor sites with an extended release rate, potentially reducing tumor size. During 2022, these clinical trials are expected to advance, and in the next decade we can expect further development in additional studies seeking new methods of crossing the BBB to advance the treatment of GBM.
Using methylation signatures to target specific routes
An important recent development concerns the number of new tools that allow oncology professionals to perform genomic classification of cancer diseases, identifying key mutations in genes that need to be addressed during treatment. By looking at genomic and epigenetic classifications, we can identify how the cells regulate gene activity. From there, we can look at the methylation profiles of genes and assess how to regulate the cellular response to therapy. The combination of methylation profiling with probiotic signatures and genomic classifications has enabled oncology professionals to identify the Achilles heel of many cancers with these specific pathways, which can cause invasion and ultimately reduce the ability of tumors to duplicate or divide.
Reuse existing medicines
Because the process of bringing a drug to market can take 10 years or more, scientists have looked at the methods by which existing drugs are administered. Recent research has shown that how the drug is administered may play a greater role in its efficacy than previously thought.
Now that we can discover the genetic, epigenetic or methylation signatures to assess pathways, we can identify existing drugs and those in Phase 1 or Phase 2 trials to reuse and link them to new local drug delivery technologies to improve efficacy . As a result of these newly discovered molecular pathways based on genomic profiling and sequencing data, we can reuse drugs that have no role in the treatment of tumors and were not considered valuable in the treatment of brain tumors.
If we take it one step further, if we use FDA-approved drugs, we can halve the time it takes to prove the safety and efficacy of a new drug to get it into the hands of clinicians for their therapeutic toolbox. . By embracing these new technologies, we have the potential to change the outcome in GBM cancer care.
Clinical trials recover from the impact of COVID-19
As oncology evolves after the challenges of the COVID-19 pandemic, we have a lot to expect. Even before the pandemic, most patients in the United States did not participate in clinical trials because of daunting logistical complications. Challenges remain, but there is greater clarity about what we need to overcome to bring greater equity and access to the cancer clinical research space for patients.
As we progress beyond the peak impact of COVID-19 on clinical trials, we need to find a way to improve clinical trial structures so that all patients with GBM, especially those affected by social determinants of health, can more easily receive care in the clinical trial setting. There is hope that we will continue to see dedicated attention from those working in this space for years to come, which will ideally open up more opportunities for patients with GBM to receive more affordable, cutting-edge treatments.
About the author
Mitchell S. Berger, MD, is the director of the University of California San Francisco Brain Tumor Center (BTC) and the principal investigator of BTC’s SPORE Brain Tumor Program. He is also a member of PolyPid’s scientific advisory board.