Metformin and LFS

Could this medication for Type 2 Diabetes help prevent cancer?

What is Metformin?

Metformin is an oral medication that decreases the amount of sugar made in the liver, helps the body use sugar and recognize the insulin receptors again. First created from French Lilac in the 1920’s to help manage diabetes, Metformin was put aside when insulin was developed. Decades later, in the 50’s the French began clinical trials and Metformin eventually became widely used in Canada, the UK and in the US during the mid 90’s to treat type 2 diabetes. The exact mechanisms of Metformin aren’t understood, but as researchers learn how it works, they get a better understanding of how the body uses sugar, how cancer cells use sugar, and if this drug could help prevent tumors.

BMC Biology: Understanding the complexity of Metformin action: limiting mitochondrial respiration to improve cancer therapy

Why Metformin for Cancer?

Doctors and scientists promote eating a healthy diet and reducing sugar intake to help prevent cancer. In 2007, researchers noticed that Metformin helped selectively starve cancer cells that did not have functioning p53. When LFS mice were put on Metformin, they grew fewer tumors. In 2008, MD Anderson began clinical trials using Metformin in breast cancer treatment, and began poring over data collected from diabetics on Metformin. They found that Metformin significantly reduced the risk of pancreatic cancer in these populations, and further studies revealed that it was even more effective as treatment in combination with other chemotherapies. A pilot study using Metformin in patients with LFS showed a decrease in mitochondrial activity and growth of tumors, similar to results seen in LFS mice. This is important for many reasons. First, mice and humans are different, so it’s important to show the mouse model and human studies correlate. Next, understanding the pathways and the way that the Metformin works is important. In LFS mutated cells, Metformin selectively affects how the mitochondrion work, therefore disrupting the supply of energy to cancer cells.

Sugar, Energy, and p53?

P53 is inactivated in half of all cancers, and scientists found that p53 is active in mitochondria and energy pathways. Since sugar control is an important part of energy pathways, they began closing the loop that links Metformin to p53. Studies revealed p53 as a player in energy metabolism, not just tumor suppression. This makes sense if we think in a broader picture of how cancer works. Cancer cells are multiplying with abandon, to do so, they need extra sources of energy. What’s a great source of energy- simple carbohydrates- sugar! PET Scans make use of this concept by injecting radioactive glucose and using a CT to visualize the uptake. The theory is that cancer cells need the sugar and take it up faster than normal cells- hence lighting up on the scan and indicating a potential cancerous growth.

I have LFS. Will Metformin Prevent Tumors?

Metformin prevented tumor growth in mice with LFS in studies. Tumor growth is a multi-step process. Cancer cells are tricky and like to find their way around medicine designed to stop them. The initial results are very promising, but like any medication, Metformin may not be good for everyone. It is best to discuss the risks and benefits of taking Metformin with your medical team. They know you and your medical history the best and can help determine if Metformin might benefit your current regimen.

How is Metformin Taken?

Metformin is a pill taken daily with meals. The dosage will depend on factors such as tolerability and side effects. It can be taken in doses of 500mg up to 2000mg. Most people start with 500 mg and increase the dose until it reaches therapeutic levels, usually at 1,500-2,000 mg.

What are the Side Effects of Metformin?

The most common side effects of Metformin are nausea, stomach pain, bloating, gas and diarrhea. These effects usually are temporary but some people experience severe effects. This is one of many reasons to be in communication with a medical professional when starting this medication.

Are There Risks with Taking Metformin?

There are some risks with taking Metformin. These risks are generally rare. It can increase the risk of low blood sugars, risk of kidney or liver damage and a condition called lactic acidosis. The risk of kidney damage can be increased with certain other medications and contrast agents, so it’s really important to let all providers know if you are taking metformin. Also, over time Metformin can deplete B12 absorption, so it is important to monitor these levels if you continue to take Metformin.

Where Can I Get more Information on Metformin and LFS?

Here are some resources to learn more about Metformin and its use in cancer prevention.

Pilot Study of Metformin in LFS Patients:

Safety and Tolerability of Metformin in LFS Patients:

Cell Stress in Mouse Models:

Metformin and LFS Mice:

A Diabetic Perspective on Metformin:

An LFS Patient’s Experience in the Metformin Clinical Trial:

Mutants Vs. Radiation: Trying to Understand Radiation in LFS

Generally, everyone should be cautious around radiation, but also realize radiation is all around us.

When we are diagnosed with LFS, one of the first things we are cautioned is to avoid radiation. So what exactly does this mean? Should we avoid dental x-rays? What about the airport scanners? Do cell phones cause cancer? Can we eat bananas? Did you even know bananas are radioactive? It has to do with the Potassium in bananas, there is an isotope of Potassium that decays and periodically releases radiation, measurable by radiation sensors. You would have to eat millions of bananas in one sitting to get radiation sickness.

More about banana radiation if you are interested:  Banana Radiation

We have a saying among Mutants- fight the shark closest to the boat. Meaning, we face tough decisions with no clear answer and many complicated factors. We have to make decisions for the most immediate problem, with the resources and knowledge we have at the time. No sense in worrying about the shark a mile away if the shark next to the boat is gnawing off your leg. Radiation is used in many different ways when diagnosing and treating cancer. This becomes an issue for those of us with LFS. It is helpful to try to understand what radiation is and how it works so we can make the best decisions for us in each situation. LFS experts recommend treating the cancer you have when it comes to radiation, but to avoid it for screening.

What is Radiation?

On a basic level, radiation is energy in the form of waves or particles. It occurs naturally, from the sun, soil, rocks and even the air can contain radon. This energy is all around us and is considered background radiation.

Radiation can be low energy, non-ionizing  and cause little damage or high energy, ionizing and able to induce gene damage. There are many different strengths, naturally occurring and man made.  Man made sources of low energy radiation are radio waves, microwaves, and infrared light. These forms are blocked pretty easily with paper, skin or wood. Link here for DIY tin foil hat- I’m kidding.  High energy radiation are tiny particles with mass, however small and can penetrate through different media. The man made versions we are most familiar with are X-rays, CT’s and isotopes used for therapy.

People with LFS have Radiation Sensitivity, what is that?

Radiation sensitivity means we are more susceptible to damage by radiation due to our already mutated TP53 gene. We know that radiation and some chemotherapies work by damaging the DNA, hence calling in p53 to help fix or mark the cell for death(apoptosis). If our p53 is mutated, it doesn’t always do the job it should. Over the years, clinicians noticed that some people with LFS had cancers that were resistant to radiation and some chemotherapies. They also noticed a higher number of second tumors in the radiation fields of LFS patients. Depending on the type of p53 mutation, some cancers are more resistant or sensitive to radiation than others. Just like there are many factors that can contribute to how cancer develops, there are many factors in radiation sensitivity. What mutation, how much exposure, the strength of radiation and the type of radiation.

What’s a Mutant to DO?

Unfortunately none of us have gotten superpowers(YET!) from radiation. There have been reports in the support group of second cancers after radiation in the radiation field. Remember, there are multiple factors that lead to a normal cell turning into cancer. We have mutant p53 which could be considered one factor to begin with, being hit by something toxic like chemicals or radiation is another.  There is a fair amount of bad luck in the process- although certain tissues are more susceptible to damage, we can’t predict future cancers. Of 10 people in the group who responded about receiving radiation as treatment for various cancers, 3 had sarcomas develop within 3-10 years. Up to 2 years after treatment, one member developed recurrence and metastasis and another had necrosis and scarring from radiation.  So half who had radiation had future problems, the other half did not and one member was 25 years post radiation without any radiation related cancers. Now remember- we don’t know which type of tumors these were, what kinds of radiation were used and many other factors. The effects of radiation aren’t always just bad.


There are risks to scans that use radiation, like x-rays, CT’s and PET scans, but there is also a risk to letting a cancer go untreated.  That is the hard part of our risk vs. benefit decision. Often times the benefit of the treatment outweighs the risk.  It’s like trying to choose between a tumor and a hard place. It is important for your provider to get the information they need to make a decision about your risk. It is also very important for you to advocate for the least amount of radiation possible to get that information. Sometimes the dose may need to be adjusted to be lower specifically for you.

There is also a element of what you can live with. These are all important parts of the decision making process. Our cancers are as individual as we are. Sometimes, even with our mutation, radiation therapy might be the best option for killing the threat. Today, with proton therapy, stereotactic radiation and gamma knife, radiation treatment is more specific and targeted, minimizing damage to healthy tissues. For mutants, this is important, we do not want to create more mutations that could develop into cancer.


Get a second, third, fourth opinion. Get as much input from professionals that can help you make your decision. Try and make sure at least one of these professionals is knowledgeable in LFS. LFS CARE Community

Talk to others who have been there about their experiences. Support groups online are a good place to do this. Living LFS ONLINE Support Groups

Decide what is right for YOU. What can you live with? Everyone is different, the right option for someone else may not be the best option for you. Take your time to make the decision and weigh all the risks and benefits.


For More Information:


Chem Cases- Nuclear

2017 Screening Recommendations for Li-Fraumeni SyndromeLast year, in October, Li-Fraumeni Syndrome(LFS) experts from all over the world met to form a panel…Aug 24


Comparing MRI vs PET/CTJust yesterday in the support group, there was a question about the difference between PET scans and…Apr 29

The Shark Closest to the BoatMy husband laughs that I often mix up my idioms. It’s not rocket surgery I tell him. A few years ago…Mar 25