Dr. Lewis Cantley is Director of the Cancer Center of Weill Cornell Medical College and one of the leading authorities on the hypothesis that the metabolic defects observed in cancer can be exploited to prevent, slow the growth of, and even treat cancer. In this brief interview, Cantley reviews key elements of his research and explains his understanding of the links between cancer, diabetes, and metabolic disturbances.
Cantley discovered PI3K and by the early 2000s argued this enzyme was a key moderator of the downstream intracellular impact of insulin and insulin growth factor signaling. This discovery later expanded to an interest in how various growth signals — like that of insulin — stimulate tumor growth, and how their inhibition (either by pharmaceutical means or removing the cause of their upregulation — i.e., reducing insulin levels) can slow tumor growth. He observes:
As we acquire tools that allow us to acutely knock out or knock down the expression of a particular gene, or have a drug that inhibits a particular step in a metabolic pathway or signaling pathway, we are finding that the system responds to these perturbations by attempting to reactivate the pathway. In other words, a lot of what we call robustness in nature comes about because biological systems have numerous negative feedback regulatory networks that sense when the system is out of balance and become altered to restore homeostasis.
The interview closes with a discussion of the unique role of fructose in metabolic disease. Cantley explains that fructose is metabolized entirely differently from other carbohydrates. Because of these metabolic differences, fructose is primarily stored as fat rather than used as fuel by the brain or muscles. This mechanism made sense long ago in humans’ evolutionary history when it was desirable to store fat at the end of a growing season, but it has become maladaptive as our levels of fructose consumption increased. This, combined with the addictive properties of sweetness, leads to fat storage and metabolic disease.
The consequence of people eating lots of sweeteners, no matter what they are — whether they’re natural or unnatural — is that it increases the addiction for the sweetness. As a consequence, at the end of the day, your brain says, ‘OK, at some point I need some glucose here.’ And then you eat an entire cake, because nobody can hold out in the end. The only way really to prevent this problem — to break the addiction — is to go completely cold turkey and go off all sweeteners — artificial as well as fructose. Eventually the brain resets itself and you don’t crave it as much.