Glioblastoma Brain Cancer – An Incurable Cancer?
Before I begin reviewing this great article I think it’s worth mentioning that this work was supported by the Swedish cancer society. So all of you who are posting no make-up selfies and donating money to cancer research, your money is likely to be funding research similar to this in your home country! If you are really interested in finding out where this money goes, read on.
This recent paper in the journal Cell, published by a team in the Karolinska Institute in Sweden, shows the latest development in the fight against cancer. In this paper, researchers investigated one of the worst types of brain cancer; the Glioblastoma. This form of cancer develops from mutations in glial cells in the brain. Glial cells have normal functions in your brain and are as important as those precious neurons in ensuring that your brain functions properly.
I actually study glial cells myself so I’m going to take advantage of this opportunity to briefly explain, list these other brain cells and what they do. There are several different glial cells in your brain; Astrocytes, which have many functions and can act as the garbage men in the brain, cleaning certain neurotransmitters from synapses, as well as providing energy to neurons because they form the link between blood vessels and neurons; another glial cell is the Microglia which acts as the immune cell in the brain, these cells scan the brain for abnormal cells and if it finds them it is fully prepared to take care of business; there are also Oligodendrocytes, cells which form the myelin, a substance which coats the axons of neurons allowing them to fire properly and efficiently; and finally there are NG2+ cells, these cells are quite mysterious, we know they can become oligodendrocytes when needed but their other functions are not so clear. For further reading I would recommend this brilliant book by two great scientists I have had the chance to meet several times.
Back to the paper in question, the researchers are investigating one of the most severe forms of brain cancer, it is effectively incurable and if you are unfortunate enough to get this cancer the outlook isn’t great with only 3-5% of patients surviving more than 3 years. This is pretty scary, and really shows the importance of cancer research. On another side note, there is a lot of misinformation regarding cancer and I have spoken with family members about this, so I highly recommend taking a look at an article by Cancer Research UK where they debunk 10 cancer myths.
In glioblastoma brain cancer it is believed that the cells which become mutated are glial cells, more specifically astrocytes and oligodendrocytes. These mutations are both gain- and loss-of-function. A gain-of-function is basically putting the accelerator on cell growth and division, the cells keep reproducing themselves to make more and more mutated cells. A loss-of-function is when the foot gets taken off the breaks, which means that the safety mechanisms in place which cause cells to die etc. are no longer active and cells live abnormally long lifetimes. This is what makes these glioblastomas difficult to treat, there are many different mutations involving multiple cellular pathways. However, these scientists hypothesised that due to all of these gain- and loss-of-functions, these glioblastoma cells probably have properties which are different to normal, healthy cells and we might be able to take advantage of this to kill them off.
In this paper, researchers grew glioblastoma cancer cells in a petri dish and exposed them to hundreds of different molecules one at a time to see if any of these molecules could reduce the size of the cancer cell or kill them. Following this screening process, it was discovered that one molecule, they name Vacquinol-1 was the most efficient at killing glioblastoma cancer cells without having a big effect on other normal cells, in petri dishes. It was found that this drug didn’t have any effect on other types of cancer cells such as breast and prostate cancer cells, so it is specific to glioblastomas.
(Here you can see the effect of the drug. Starting on the left we have the normal glioblastoma cell, moving to the right the drug is added and as you can see the effects are immediate, finally resulting in cell ‘bursting’ and death after 440 minutes; Vacquinol-1 treatment in a petri dish. (Image source: Kitambi et al. 2014)
Following this work in petri dishes, the authors moved to a more physiological model using mice which have had human glioblastoma cells injected into their brain. They had two conditions, one where the mice were injected with Vacquinol-1 into the area where the glioblastoma cells were injected and the other group receiving injections but without the drug. They found that mice brains which received Vacquinol-1 has far less tumour progression that those which didn’t receive the drug. Glioblastoma cancers are also very bad news for mice which also die soon after injection with the cancer cells. It was found that mice which were injected with the cancer cells and received treatment with Vacquinol-1 could survive a lot longer. During the 80 day experiment it was found that all 8 mice who didn’t receive the drug didn’t survive longer than 31.5 days whereas only 2 out of 8 mice in the group receiving the drug died after 80 days. This is a really strong finding.
Up till now I have still held onto my reservations because it is well-known that a lot of drugs never reach the market because they are unable to get into the brain. The blood vessels which go into your brain are tightly controlled and most molecules cannot cross what we call the Blood-Brain Barrier (BBB). However, Vacquinol-1, which is quite a small molecule (according to the authors) was able to get across the BBB and into the brain which one of the greatest barriers for any drug.
This drug, Vacquinol-1, seems quite the wonder drug as far as glioblastoma cancer is concerned. This is the very first study investigating this molecule for this purpose and as such has received a lot of attention. It still remains to be seen if this drug could possibly work in humans. Yes, it did kill human glioblastoma cells in mice brains but will it work in human brains? We should also be wary of other possible side-effects which we are unable to see using mice models, mice cant exactly talk to us and tell us how they feel after taking a drug. It still remains to be seen whether this drug will be able to pass as easily into the brain in humans; mouse and human biological systems are quite similar but we shouldn’t take for granted that we are the same.
I believe that we will be hearing a lot more about this drug in the future. However, it is important to keep in mind that this drug is in the beginning stages of research and many more years will be needed before we will possibly see Vacquinol-1 appear on the market. This paper is really great and should give us hope for future cancer treatments.
