I am a scientist studying evolutionary genetics, an important but fairly abstract discipline. Several years ago, I witnessed a vibrant, active middle-aged woman succumb to an aggressive form of cancer. There was nothing that doctors could do, and within just a few months, she was gone.
During the months of her rapid decline, I kept thinking how good we are at treating early-stage tumors, but the treatment of advanced cancers continues to elude us. How is it possible that, with all our knowledge, we remain relatively powerless against aggressive, metastasizing tumors?
My team and I believe there may be a way.
Our goal is to develop treatments that target not genes and proteins but an overlooked vulnerability — the tumor’s dependence on glucose.
Most cancers use large amounts of glucose. (Glucose levels are used by PET scans to find, diagnose, and grade tumors). We aim to stop tumor cell growth by restricting the amount of glucose available. While it is a fairly straightforward idea, it is difficult to implement because there are several sources of glucose available to the tumor. We can limit glucose via a ketogenic diet (i.e. restricting carbohydrates). But a keto diet is insufficient as our bodies can make plenty of glucose from fats and proteins. Fortunately, there is a widely-used medication, metformin, that is used to treat diabetes. Metformin decreases glucose production in the liver and has very tolerable side effects. By combining a ketogenic diet with metformin, we can reduce the total amount of glucose available to tumor cells and essentially starve them.
Will this treatment damage normal cells and tissues? Fast growing tumors lack sufficient blood supply and lack sufficient oxygen. These “hypoxic” tumors use a somewhat crude method to extract energy from glucose, so they need vast amounts of glucose to sustain themselves. Normal tissues, however, use products of fat and protein metabolism for energy — instead of glucose. Based on this, we can decrease the amount of glucose that a tumor needs to survive without damaging normal cells and tissues.
We actually know that this method works. My team and I have already conducted pilot experiments that confirm these outcomes. We maintained mice on a diet with no carbohydrates and dosed them with an amount of metformin equivalent to a normal human dose. Blood glucose levels decreased to about 60% of normal without causing signs of distress in the animals. (The animals were carefully observed and strict regulations were in place to ensure their wellbeing.)
The next step — this project — is to test the combination treatment on a triple-negative breast cancer mouse model. We won’t inject tumors or carcinogens into the mice; rather, we will try to cure the tumors that naturally occur. My team and I will conduct pre-clinical testing to see if our combination of diet and metformin can prevent or slow down the appearance of tumors in these animals. Results from these animal studies will inform future clinical trials in humans.
Our initial experiments show great promise. Please help us continue our research, hitting cancer where it hurts.
Why is this important?
We are working to provide a badly-needed treatment option for later-stage, aggressive cancers.
There are a number of successful treatments for early-stage tumors occurring in one location, but they do not work as well for later-stage, aggressive cancers. Hypoxic tumors (tumors which, because of their fast growth, need more oxygen than surrounding tissue can provide) prove to be particularly resistant.
Even if this therapy would only partially work for a patient, delaying the spread of cancer for several years, it would be a significant step forward. Additionally, this approach could be combined with other, established therapies.
Who will benefit?
Everyone battling a later-stage, more aggressive breast cancer could potentially benefit from this new therapy.
To start, we will focus on treating triple-negative breast cancer (a type of cancer which occurs in about 10-20% of breast cancers), using mice to model the therapy. If the approach is successful with this tumor type, we will expand to other types of cancer.
Ultimately, our aim is to provide patients with late-stage tumors another weapon in their arsenal to fight cancer and a greater chance of long-term survival. Please help us continue our research.