Hello again. We return today to discuss MGMT Methylation.

MGMT Methylation is a little tricky; but stick through to the end of the video and I hope you are better informed and able to talk with your medical team and family with improved understanding and what is the importance of MGMT methylation on your pathology report.

What is MGMT Methylation? This is one of the first and early tests you should receive on your tumor. I think it should be automatic, but it may not be the default that this test is completed or that you are informed of the result. I requested this test to be completed and to receive the results. MGMT is Methyl guanine Methyltransferase. That is a real mouthful I know. Methylation, in a nutshell, is whether a gene is turned on or off. We will discuss this in more detail later.

After surgery and recovery, your first treatments with Glioblastoma will likely include Chemotherapy. The most likely version of this is Temozolomide. It is one of the most significant breakthroughs in GBM treatment in the past 10 – 15 years and may provide additional weeks of life expectancy. There are not a lot of drugs that can make it through the blood-brain barrier. Your brain is protected by the blood-brain barrier so that harmful substances, such as viruses, bacteria, or other nasties find it difficult to get into the brain. This works to our advantage most of the time.

But when we are trying to deliver drugs to the brain to attack the brain cancer the blood-brain barrier prevents most options from working efficiently. Some Temozolomide can make it through the blood-brain barrier and as a result, it can work as a chemotherapy drug. It is designed to work best to take it while undergoing Radiation Therapy. The two treatments may work together in synergy to a greater effect than either one on their own. As I said earlier, Temozolomide may provide additional weeks of life. But, for others, it may provide more or, less time. It may keep the cancer at bay if it is effective. We will discuss this further in the Temozolomide video which you can find on my channel.

The topic of MGMT can be confusing so feel free to watch this video multiple times to come to a clear understanding. It is helpful to understand that we all have MGMT genes in our bodies. It is either methylated or unmethylated. Unmethylated means the gene is active and the MGMT works as it should in the body. Methylated means that the MGMT does not work as it should in the body. If we have GBM we want our MGMT to be Methylated i.e. NOT working.

Back to MGMT Methylation. Due to large variations in different studies, we know that about 30% to 60% of GBM patients will be MGMT Methylated. If you are one of these people it can be an advantage. DNA is made of 4 letters GTA and C and the target of Temozolomide is the G. In the DNA of the GBM cancer cells, Temozolomide attaches to the G (guanine). The Temozolomide molecule attaches to the ‘G’ and prevents the DNA strand from synthesizing or (reproducing). Additionally, Radiation Therapy also damages the DNA of cancer. If you have unmethylated MGMT both the damaged DNA from the Temozolomide and the damage that was caused by the Radiation Therapy will likely be repaired by the body by using the MGMT enzyme. The MGMT enzyme will strip the marker off the G (guanine) and stop or reduce the effectiveness of the Temozolomide. This is why unmethylated MGMT in Glioblastoma equates to a poorer prognosis.

MGMT is a protein or enzyme that repairs DNA. If unmethylated MGMT sees the Temozolomide molecule attached to the ‘G’ (Guanine) it will strip it off rendering the Temozolomide mostly ineffective. Imagine that the ‘G’ has a hat on it and that hat causes the DNA not to be able to reproduce and instead causes it to die known as cell apoptosis.

The unmethylated MGMT goes around and finds any ‘G’s’ with hats on them and it removes the hat. If we are taking a drug to help kill the Cancer by attaching to the Guanine and preventing the DNA strand from reproducing we do not want this to be prevented by our body’s own system.

What does Methylation mean? A gene has two ends to it, a promoter end and a functional end of the gene. If the promoter end is methylated it is turned off. As a result, the functional end of the gene does not work. If a Glioblastoma tumor is methylated it means that the MGMT protein is NOT being produced and therefore the molecule will NOT be removed from the ‘G’ (Guanine). Essentially, the Temozolomide that successfully makes it to the cancer cells are NOT stripped off and can do their job.

This is why it is important to know if you are MGMT Methylated positive or negative. You want to be MGMT methylated Positive.

MGMT-positive patients in the Glioblastoma population had significantly longer overall survival which is usually abbreviated as OS when compared to MGMT Methylated – Methylated patients example Overall Survival 32.8 months versus 12.4 months for Unmethylated patients.

If you are not MGMT Methylated positive do not lose hope or be too disappointed. Although the prognosis is improved for approximately 30% to 60% of GBM patients with MGMT Methylation it is not the only factor that may help. There are other steps you may be able to take. Each of these steps is time-sensitive and they have been important to me.

Remember, Glioblastoma is incredibly challenging; but, with some knowledge and understanding, we may increase our odds of fighting this terrible disease.

I encourage you to watch the other videos in this series and become knowledgeable so you can make informed decisions with your medical team, family, and friends.

It should also be noted that if you are MGMT unmethylated, Temozolomide may still have a beneficial effect and for some people, this could be important. There is no way to know unless you try. The information above gives you both a better understanding of how it works and the probabilities of being MGMT Methylated positive or negative but there is no definitive answer here. People will react differently and this is why I always encourage you to learn all you can and then make informed decisions with your medical team, family, and friends.

There is a lot of technical information in this video so watch it as many times as you need to get a good understanding and then discuss it with your medical team, family, and friends.

To help make these videos possible please subscribe to my channel, watch each video to the end, click on the like button in each video, ask your family and friends to do the same as this is fortunately not a large community of people with GBM. Additionally, any products that I suggest or recommend are linked below to which I may receive some proceeds at no additional cost to you to help with the costs of these videos. Also, if you feel compelled or if you can help please log onto my Patreon page as seen on-screen. You can provide a gift that will assist me in making these videos. Please leave any positive or encouraging comments below and remember this is information I have learned, and it is helping me; it may or may not provide benefit to you. God bless you, I hope you find these videos are helpful and can make a difference in your life. Please consult your medical team before following any steps I have taken on my journey. I will see you in the next video.