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: https://clinicaltrials.gov/ct2/show/NCT01981525

Safety and Tolerability of Metformin in LFS Patients: https://cancerres.aacrjournals.org/content/76/14_Supplement/CT156

Cell Stress in Mouse Models: http://www.cell-stress.com/wp-content/uploads/2019/03/2019A-Donnelly-Cell-Stress-Advanced-Pub.pdf

Metformin and LFS Mice: https://tp53.co.uk/2016/12/14/metformin-and-lfs-risk-reduction-in-mice/

A Diabetic Perspective on Metformin: https://diatribe.org/everything-you-always-wanted-know-about-metformin-were-afraid-ask

An LFS Patient’s Experience in the Metformin Clinical Trial: https://www.livinglfs.org/participating-in-a-study-deb-shares-her-story-and-about-her-trip-to-nih/


Working with LFS: When Your Brain Gets in the Way

by Fannie Lemay

I always loved to work. Even when I was cutting carrots at IGA for a living, I loved it. Well, maybe “love” is a strong word, but I still really enjoyed myself. I’m what you would call a power loner. In my personal life, I have few close friends and that’s how I like it. I’m an introvert; I’m not outgoing. But for some reason, it’s easier for me to connect with people when I’m at work. I’m a bit silly and it seems to bring people together. I work hard and I like taking care of my work family. A lot of my self-worth comes from work. I don’t doubt at work; I just do. Well, I did…

First Christmas party at Cossette in 2010 with my favourite proofreader spectacular Geneviève. She taught me basically all I know.

When I started working at Cossette as a translator a little less than 10 years ago, it was my dream job. When people asked me during my college years where I’d like to work once I was done, my answer would always be “in the advertisement”. Of course, back then, I had no idea what it really meant. Luckily for me, the advertising world seemed to fit my personality and my brain perfectly. I was fast and could take the pressure. I found a very patient mentor that taught me to be a decent enough translator to keep my job, and I became part of an amazing AMAZING team that helped me become a better version of myself. Two years later, I became the team’s coordinator, and that was the best gift I ever received.

My brain was perfect for this new job. Because you see, my brain doesn’t work quite right. I have hyperesthesia, which basically means that sensory information reaches my brain faster than the average, and the information is processed in a significantly shorter time. My senses are basically heightened. Having hyperesthesia has a lot of disadvantages. Some days, I can’t stand being touched even by my loved ones. It feels like my skin is burning. I can’t tune out any sounds, so I have to work with headphones or the A/C will drive me insane. If my son is noisy, sometimes I have to leave the room for a while so I don’t get too irritated. I’m very rigid with food brands and if someone removes their shoes, I can smell their feet even if they don’t stink. It just smells like clean feet. Sometimes having hyperesthesia is overwhelming, but most days, it’s a blessing.

My weird brain helped me a lot in my role as a coordinator. Since I had an exceptional memory, I could manage a lot of projects simultaneously without needing to take notes or setting reminders. I loved going the extra mile to make sure everything was running smoothly, and I tried to protect my team and the work we were doing with all my heart. Because you see, working in an ad agency is a totally bipolar experience. I’m not sure how to describe it… It’s just so hard and so easy at the same time. It’s great and horrible. I always say it’s not a real job, except, fuck, it is. And I love it. And it seems to

My brain post-surgery. My neurosurgeon described the cavity left by the removal of my tumour as gigantic.

like me too. Well, it did…

When my neurosurgeon showed me the MRI of my avocado sized tumour, I thought my life was never going to be the same. But, turns out, that’s not what happened at all. Three years later, my life is pretty much exactly the same. I, on the other hand, am not. I am in pain almost all the time. Most days, I can deal with it. Some days, I can’t. Even now, more than one year after my last treatment, I’m still exhausted pretty much all the time. The kind of exhaustion that makes your legs hurt. Some weeks, I can have three “good” days in a row and, if I’m lucky, I can pull a fourth one out of my ass, but then I pay for it and I’m stuck in bed for 24 hours. Because my body never lets me forget that I’m broken. That this shitty treatment broke me.

My brain is also damaged. You can’t really tell from the outside if you don’t know me (or maybe you can), but it is. People tell me it’s just part of getting older, like chemo and radiation had less impact than the passing of time. Like I somehow aged 10 years in 12 months. I guess they want to make me feel better or more normal. It’s not working. Not even a little. But they mean well, so it’s nice. But I have to take notes now. All day, every day, I take notes. So I don’t forget. I FORGET STUFF NOW. A LOT. Not a lot actually, but a lot more. If I get interrupted, I lose track of what I was doing sometimes. When it happens, it hurts me, deeply. I was always able to rely on my brain, but not anymore.

All of this made my return to work very difficult and emotional. I’m not the same Fannie that left Cossette two years ago. I can still work and my new team seems to think I’m doing well. They are awesome and understanding. They are insane, and human and lovely. They laugh for real and eat cookies in the middle of the week. They are a little haven in this crazy place that is Cossette. I like them. But every time I forget something or miss something I wouldn’t have missed before my treatment, it hurts me. A lot. When I have to go home at 3 pm. because I’m too exhausted to do a good enough job until 5 pm, it hurts me. When I can’t be warm with my coworkers because the damn voice in my head screaming CANCER is just too loud that day, it hurts me.

This is Louise. She’s basically the soul of Cossette. She helped me feel confident that I was still worthy of keeping my job when I was at my lowest. I will be forever grateful to have had met her. I know returning to work is hard for any cancer patient. Some of my dearest friends had to go back to horrible working environment where they were judged and bullied. It’s not my case. I am very lucky to have landed in a company that takes care of me during this trying time, but it’s still hard. I guess I still have to make my way to the fifth stage of grief: Acceptance. When I started to live with Li-Fraumeni Syndrome, I had to let go of a lot of things. My freedom, my breasts, my innocence, having more kids, the ability to stay awake past 9 pm, my hair, but also, my career. I can’t seem to let go of what I thought my life would be. I have to redefine what I am as a wife, a mother, and an employee so I can be done with the constant guilt. But it’s hard you guys. It’s fucking hard.

If you are living with cancer and about to go back to work, I hope you can find a place that welcomes your new normal. Because let’s face it, you have other stuff to be worried about. Also, be kind to yourself. You are still worthy and your journey probably made you a better human in a lot of ways. That’s a very special gift. And if you work with someone that has a chronic disease, please be kind. Sometimes, you can’t tell from the outside how much they hurt inside…

Interesting fact: Cossette is the ad agency responsible for creating the amazing campaign for Sickkids. The Sickkids Foundation is a very important institution for the Li Fraumeni community. This is Sickkids VS Undeniable, one of the most powerful spots I have ever seen.