Targeting Cancer's Sweet Tooth: The Links Between Insulin, Sugar, and Cancer Growth

The Discovery of PI3 Kinase Signaling in Both Insulin and Oncogenes

In the 1980s, Dr. Lou Cantley made a breakthrough discovery regarding an enzyme called PI3 kinase. He realized it was a key player in insulin signaling that helped cells take up glucose. But he also found that PI3 kinase activity was increased by oncogenes – the mutated genes that drive cancer growth.

This suggested an intriguing link between insulin and cancer. Insulin tells our cells to grow and divide while taking up nutrients. Many cancer cells hijack the normal growth pathways that insulin controls. This can allow cancers to grow faster, especially in environments with chronically high insulin.

The Introduction of High Fructose Corn Syrup and Rise of Obesity

In the 1960s, high fructose corn syrup was introduced as a new low-cost sweetener derived from corn. This allowed cheap, sugary soda pops and juices to flood the market. As a result, sugar consumption greatly increased.

Dr. Cantley witnessed this firsthand growing up in rural West Virginia. In the 1950s, obesity was extremely rare there. But after high fructose corn syrup arrived, obesity rates steadily climbed over the next decades.

Seeing this crisis unfold, Dr. Cantley eliminated sugar and desserts from his own diet in 1975. At the time, the role of metabolism in driving obesity was still poorly understood. But years later, Dr. Cantley’s research began to unravel the mechanisms linking sugar to cancer.

Colorectal Cancer Growth Accelerated by Glucose and Fructose

Recent experiments have shown that feeding mice a high sugar diet dramatically accelerates growth of colorectal tumors. The effect depends on the presence of both glucose and fructose together. If either sugar is missing, tumor growth is not enhanced.

Liquid sugars are particularly damaging because they can reach the colon undigested. The fructose arrives intact and gets rapidly phosphorylated by colon cells, draining ATP. This energy depletion causes cells to take up the co-delivered glucose and shunt it into anabolic growth pathways like fatty acid synthesis. So the fructose cripples energy production while the glucose provides the carbon skeletons needed to construct new cancer biomass.

Insulin as a Master Growth Hormone for Both Normal and Cancer Cells

As decades of research revealed, insulin exerts its effects on cells by activating PI3 kinase. This stimulates nutrient uptake and growth. Many cancer cells co-opt this pathway to drive their own proliferation.

Insulin resistance leads to higher insulin levels as the body tries harder to control glucose. This hyperinsulinemic state likely accelerates cancer growth. Pancreatic and colon cancers often mutate PI3 kinase to become hypersensitive to insulin. So insulin resistant individuals may grow tumors far more aggressively.

Controlling the Insulin Spike – A Key Challenge for PI3 Kinase Inhibitors

Drugs that inhibit PI3 kinase slash cancer growth rates. But they also cause severe hyperglycemia since insulin signaling is crippled. In response, the pancreas dumps large amounts of insulin into the blood. So while PI3 kinase is blocked in tumors, insulin reactivates alternate growth pathways.

Combining PI3 kinase inhibitors with other glucose-lowering agents like metformin or SGLT2 inhibitors prevents this insulin spike. It enhances anti-tumor effects. Putting mice on a low-carbohydrate, high-fat ketogenic diet is also very effective. Without dietary carbs, insulin remains low even while taking PI3 kinase inhibitors. Starved of insulin’s growth-promoting signals, cancers shrink and die.

An Evolutionary Perspective on Sugar Addiction

When sugars were only seasonally available, bingeing on them in the fall could provide precious fat stores to survive winter famine. So humans likely evolved strong reward pathways and cravings driving overconsumption of sugars whenever they appeared.

Today, we have constant access to concentrated sugars year-round. Our ancient biology still compels many to binge, like bears preparing for hibernation. But while bears safely sleep off the metabolic effects, the chronic hyperinsulinemia caused in humans appears to feed many cancers.

Potential Public Policy Actions to Curb Metabolic Disease

Data continue accruing on the metabolic havoc and cancer growth driven by excess sugar intake. But sugary foods and beverages remain ubiquitous. Some potential public health measures may include:

• Reduced marketing and advertisement of sugary products to children
• Taxation on added sugars, especially in beverages
• Improved food labeling showing added or free sugars
• Public health campaigns educating on metabolic disease risk

Change cannot rely solely on individual behavior. Past anti-smoking efforts required coordinated policies targeting advertising, taxation, and education. Similar broad efforts may be needed to curb the overload of low-cost liquid sugars now pervading modern diets.