Glioblastoma Multiforme: the Perfect Storm

Yesterday was a strange day. I have read that due to COVID-19, the average life expectancy has dropped by about a year. It now stands at 82 years (79.7 years for men and 84.4 for women). At the same time, I read that investments in start-ups that promise life expectancy by reversing aging are increasing and to invest in these start-ups are the super rich like Bezos. There is indeed a paradox … the young want to become rich … the rich want to become young again.

An interesting point to think about is that working on the Yamanaka factors (which seems to control ageing) and trying to reprogram the cells to make them rejuvenate carries with, it for the moment, the risk of generating tumours that instead kill you.

Personally I would first try to defeat the tumors and then I would try to extend life expectancy even if obviously the different researches are not one alternative to the other. I would also like these drugs that promise longevity to be accessible to all … even if I know perfectly that this is unrealistic and certainly for a period they will be accessible only to the super rich, then to the rich and finally to mere mortals.

There is a disease that is very democratic because it affects everyone, rich and poor people: it is glioblastoma multiforme.

There is still no cure for glioblastoma, but the standard of care that has been in place for over 10 years is starting to change, as evidenced in a number of promising studies.

Among tumors, glioblastoma can be considered a kind of perfect storm. It grows rapidly and is found in the brain, the most protected and delicate part of the human body. This means that surgery must be done quickly and few drugs can reach the tumor due to the impenetrable blood brain barrier.

Furthermore, the cells are heterogeneous, which means that each must be individually targeted to slow tumor growth.

Surgery has a hard time removing all the cancer because of the way the tumor diffuse into the brain, so the tumor starts growing again soon after the surgery.

The median survival rate is 15 months with treatment and less than 6 months if not treated according to the National Cancer Institute. Even though the five year patient survival rate is about 6%, they are likely never to be considered cancer-free and remain on radiotherapy and chemotherapy for the rest of their lives.

The tumor creates new blood vessels as it grows and can accumulate dead cells in its nucleus. We still don’t understand what causes GBMs.

What is known is that glioblastoma is not hereditary, is diagnosed in adults more than in children, and is slightly more common in males.

There are studies that have presented evidence linking cancers to cell phone use, radiation exposure, or work in certain professions.

The number of studies and research focusing on the cause and treatment of glioblastoma has skyrocketed over the past decade as has the value of the market for glioblastoma treatments, medications and therapies.

It was the multi-million dollar Cancer Genome Atlas project that confirmed the difficulty in treating glioblastoma. No two cancers are alike and this means that no patient has exactly the same form of cancer.

The biggest breakthrough in the fight against glioblastoma came in 2002, when the FDA approved temozolomide for use in patients.

This is the chemotherapy drug that patients take after surgery and radiation therapy.

It is also one of five FDA-approved drugs to treat glioblastoma, along with lomustine, intravenous carmustine, carmustine wafer, and bevacizumab (Avastin). Other drugs are approved in other countries such as Regorafenib which is used in Italy.

However, standard treatment is not currently a cure as it is only capable of slowing the progression of the disease except in rare cases.

A group of Columbia University researchers recently managed to define four different categories of glioblastoma based on its key biological characteristic.

The group called “mitochondrial” could be treated by a drug that could feed the mitochondria of the cancer cell and this could affect the growth of this type of tumor.

Dr. Maria Castro of the University of Michigan is currently working on a glioblastoma vaccine that appears to work in mice for now. Infecting mice with an oncolytic virus that kills some of the cancer cells by awakening the immune system, it was noted that not only does the disease go away but if mice are injected with new cancer cells their immune systems are able to eliminate them without further treatments.

There is also a single non-invasive and sonodynamic treatment developed by researchers from the Ivy Brain Tumor Center. One drug, protoporphyrin, is administered intravenously and travels to the brain where it is metabolized only by glioblastoma cells.

Protoporphyrin is then activated by ultrasound, which stimulates photodynamic energy from within the glioblastoma cells and destroys them. The clinical trial phase started in March.

Treatment with alternating electromagnetic fields (Optune device) has proved to be the most effective development in recent years, managing to bring the average life expectancy to two years. However, this treatment requires that the patient’s scalp be shaved and the patient wears a helmet for 18 hours a day. Similar new treatments being studied also seem more effective and fortunately do not require the patient to be completely shaved or worn for that long.

In short, the diagnosis of glioblastoma is difficult to digest but the research is at work and everyone’s hope is that some of these new treatments or a combination of them targeted or designed for the individual patient and his specific glioblastoma will be able to help him/her survive the perfect storm.

Who knows, maybe this could paradoxically also help longevity studies since potential cancers stimulated by the attempt to reverse aging could be neutralized.

Finally, after these long thoughts, I ask you again and with even more force to continue to help the fundraising campaign for CUSP9v3 Phase II-III for Emanuele by sharing the link in order to spread the word and raise awareness as many people as possible .