Through Better Technology, Innovative Glioblastoma Treatment Options May End Terminal Diagnoses
Gord Downie, the frontman of the Canadian band The Tragically Hip, was given a terminal glioblastoma multiforme prognosis and chose to spend his last months touring Canada in addition to raising awareness about the disease. Recent research into the glioblastoma multiforme may end, or reduce, terminal diagnoses. Image Source: The Armed Forces Institute of Pathology
A third of all Canadian residents took an evening in August to tune into the CBC or attend a viewing party for a concert that was being broadcast from Kingston because of one illness: glioblastoma (GBM). Gord Downie, lead singer of The Tragically Hip, was diagnosed with glioblastoma last winter after he suffered a seizure. Glioblastomas are the most common form of malignant brain tumours in adults, leading to an average life expectancy between fourteen and eighteen months. These are fast growing tumours which are generally diagnosed after symptoms appear, including seizures, neurological deficits and stroke-like symptoms.1
Unfortunately, this is a terribly difficult form of cancer to treat as it is incredibly aggressive. It cannot be reached by most chemotherapy (due to the blood brain barrier) and cannot be completely excised due to the tendrils that extend throughout the brain.
However, there have been recent glimmers of hope regarding new biologic therapeutics that could target the disease. New biomarkers have also been discovered, which have the potential to lead to faster diagnosis. Moving forward, researchers will benefit from modern lab software that will help them navigate the complex nature of glioblastoma, it’s biomarkers and potential biological therapeutics.
Innovative, Novel Biologic Therapeutic Approaches To GBM Treatment
Different biologic approaches to GBM have been in the works for a number of years. Few of them have progressed to clinical trials, but in the last year a number have made it to stage II or III clinical trials. One of these approaches is a gene therapy, VB-111. The mechanism of action, like many current therapeutics in development, works by interfering with the ability to grow new blood vessels within the tumour. VB-111 had relative success in a stage II clinical trial. It was used in patients with recurrent glioblastoma who had a very short life expectancy, and was effective at extending life expectancy of patients (from eight to fifteen months) and was very well tolerated as a solo medication and in conjunction with bevacizumab, a monoclonal antibody therapy. Granted, these results are inherently biased due to the population that was administered the therapeutic, which is why it will be moving to a broader audience upon phase III clinical trials.2
Researchers can use innovative lab software to accurately identify potential sites of action in different diseases, and compare each active site against orphan drug databases to potentially save R&D dollars. This therapeutic is exciting because it is a therapy plucked from the orphan drug list. Orphan drugs are those which remain commercially undeveloped because a profitable target was not found. This type of computer analysis on existing medications mitigates many of the inevitable discovery phase investigator headaches as the therapeutic has already been produced and modifications, like fitting into binding pockets at the target tissue, can be easily identified.
Attempts at GBM Vaccines Need More Development
In addition to therapeutic treatments, a number of GBM vaccines have been in the works over the last few years. Unfortunately, in the last year one of the most successful ones fell off the radar because it didn’t appear to be translating into higher survival rates as compared to the control. This vaccine relied on a peptide of a mutated form of a epidermal growth factor receptor (EGFR) protein, EGFRvIII. Although this vaccine was not successful, researchers should not give up on this target site. EGFRvIII is expressed almost exclusively in GBM cells and not found in healthy brain cells, which means that it is possible to target just cancerous tissue and avoid damaging healthy brain tissue.3 Investigators can continue to develop this vaccine by using computer software to aid in assessment of the structure of EGFRvIII, and looking at potential monoclonal antibodies that will work to suppress this mutated form the of epidermal growth factor. For the utmost benefit, this software should also move with researchers from discovery through to the bedside, and assist in collection of data from all preclinical and clinical trials allowing for better assessment of toxicity and efficacy.
Monoclonal Antibodies to Act as Checkpoint Guards
Immunotherapy research is prevalent within cancer research, which relies primarily on the fact that cancer finds ways to evade the body’s ability to rid itself of these lecherous cells. Checkpoint inhibitors interfere with the tumour cell’s ability to signal T cells and tell them to back off. Ipilimumab and nivolumab are monoclonal antibody therapies that have already been approved for use against other cancers.
There is already some preliminary evidence suggesting that GMB could benefit from drugs of this class; a CTLA-4 checkpoint targeted antibody has shrunk brain metastases in advanced melanoma patients. By targeting programmed-death-1 (PD-1), which is a surface receptor expressed on activated and exhausted T cells, scientists are seeing increased long-term survival rates in mice with gliomas.4 These results are still in their infancy, but are pointing many researchers in the direction of checkpoint therapeutics.
Investigators will be better able to examine these checkpoints by first assessing them in silico. Software has jumped ahead by leaps and bounds in the last few years and it can ease data analysis. By scouring the hoards of patient tissue information that has accrued over the past decade, it is possible to find specific checkpoints that would be ideal targets in GBM. Once the target is identified, the unified system will collect and track data right through to clinical trials.
It’s devastating that so many lives have been lost to this horrible illness, but it is encouraging to see that the tides are turning. Canada was deeply saddened to hear of Gord Downie’s illness, but they are doing what they can to make sure that his illness will have more treatment options in the future. After the concert in Kingston, Ontario, funding has been pouring into the Canadian Cancer Agency and Sunnybrook Hospital. Researchers should make the best of this newly available funding by designing and conducting trials more efficiently.
BIOVIA Designed to Cure is a suite of process experiences supported by a common platform that helps researchers to rapidly move biotherapeutic candidates from bench to bedside. It has key capabilities in documentation and data management, which will help investigators better analyze the therapeutic capacity of monoclonal antibodies, gene therapy and provide real-time project tracking. Please contact us today to learn more about how our software options can support the efforts of your lab.
- “What we know about Gord Downie’s diagnosis, treatment and next steps,” May 24, 2016, http://www.theglobeandmail.com/life/health-and-fitness/health/things-about-gord-downies-diagnosis/article30127365/ ↩
- “Gene Therapy Doubles Survival in Recurrent Glioblastoma,” October 13, 2015, http://www.oncologynurseadvisor.com/web-exclusives/gene-therapy-doubles-survival-in-recurrent-glioblastoma/article/444721/ ↩
- “With Immunotherapy, Glimmers of Progress Against Glioblastoma,” March 8, 2016, https://www.cancer.gov/types/brain/research/immunotherapy-glioblastoma ↩
- “Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas,” June 1, 2013, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963403/ ↩