What’s going on in the body when we have cancer? The standard definition is that healthy cells mutate and grow rapidly. As the abnormal cells cluster, they form a tumor, which can spread to other parts of the body – and this gets treated with chemotherapy, radiotherapy or surgery.

It’s a description that leaves a lot unanswered. Why, for instance, do cells mutate in the first place? And how can cancer cells grow far more quickly than healthy cells? The questions aren’t trivial; if we could answer them, we would know how to prevent cancer and treat it without destroying the immune system in the process.

Several new theories have emerged that could answer these questions – and both see sugar as playing a key role in the cause and development of cancer. They build on discoveries made by German biochemist Otto Warburg in the 1920s. Despite being awarded the Nobel Prize for his research, these breakthroughs have been largely ignored since then, and the “Warburg effect” reduced to a footnote in cancer research.

Oncologists have long recognized glucose as a marker for cancer, and they use positron emission tomography (PET) scans to identify areas in the body that consume excessive amounts of it. The more glucose being consumed, the more pessimistic the prognosis.

But while conventional cancer therapy recognizes high glucose consumption is a sign of cancer, it has never accepted Warburg’s belief that it is integral to the process of cancer. However, that has been slowly changing with new research focusing on cancer’s biochemistry and the source of its energy.

The insulin connection
One of the researchers at the vanguard of the Warburg revival is Dr Lewis Cantley from the Meyer Cancer Center at Weill Cornell Medical School in New York. He’s become convinced that most cancers are caused by an excess of sugar, or, more precisely, insulin – a hormone the body releases to break down sugars from carbohydrates in our diet.

Forty years ago, Dr Cantley identified an enzyme, called PI3K (phosphoinositide-3-kinase), that he described as a master switch for cancer. It plays a key role in the body’s interplay between insulin and glucose (also known as blood sugar). If the process slows, the body becomes insulin resistant, and cells cannot absorb enough glucose for their energy needs. This is type 2 diabetes.

But if the process instead goes into overdrive, then cells – and especially mutated, cancerous cells – get an abundance of glucose, which fuels their growth, and that is cancer.

It’s exactly as Warburg saw the cancer process unfolding in his laboratory – healthy cells feed off oxygen, but cancerous cells instead feed off sugar, even though it is far less efficient. He called it “aerobic glycolysis.” In theory, the cancer cells can feed off oxygen, too, but something happens to make them prefer sugar.

That “something” is a mutation that occurs earlier in the biological process, and it happens because of an excess of insulin, Dr Cantley believes. The PI3K enzyme is mutated more often than any other gene, and he estimates it is responsible for 80 percent of all cancers, including breast, brain and bladder.

The PI3K theory is still not widely accepted, but Cantley continues researching his hypothesis, over 30 years after he first proposed it.¹

The new cancer cycle

New research, building on the discoveries of Otto Warburg nearly a century ago, shows how sugar in the diet promotes the growth of cancer, both directly and indirectly through its byproduct, lactate

Don’t forget lactate
Resistance to the theory could be because there’s something missing, as other researchers are seeing something else in the cancer puzzle where insulin plays no part at all.

Although sugar may kickstart the cancer process, another new theory suggests it’s driven by lactate, a molecule usually found in muscles that causes athletes to stiffen up after a workout and, more seriously, is also a sign of sepsis and congestive heart failure.

Warburg had also seen lactate cluster around cancer cells, but he had assumed it was a useless byproduct – biological garbage. But new research suggests that lactate is the fuel that keeps cancer cells growing and spreading.

The latest to take on the lactate hypothesis is a research team from the University of Colorado School of Medicine, headed up by Inigo San-Millan. “We discovered that lactate is a catalyst that triggers a mechanism in mutated cells necessary to continue the cancer-forming process,” he says.2

In experiments he carried out three years ago, San-Millan fed glucose to a line of breast cancer cells, which, as expected, started to produce lactate – and that increased the activity of the mutated cells by up to eight times.

But lactate may not only provide the fuel for cancer growth, it could also be the disease’s signaling system. This means therapies that focus only on glycolysis – the metabolism of glucose – may not be effective if they are started too late, once the process has already moved into a later phase where lactate plays the preeminent role.

San-Millan and his team aren’t the first to suspect lactate as the driver of cancer. Professor George Brooks at the University of California, Berkeley, first proposed his “lactate shuttle” theory in 1985, and it has been explored by other researchers who suspect lactate is a key player in various other cancers, including sarcoma3 and spinal cancer.4

Exercise cancer away
So how does this change the treatment landscape? Extraordinary as it may sound, San-Millan and his team are devising a series of personalized exercise programs for cancer patients. Although exercise is recognized as a healthy lifestyle choice to help prevent chronic disease, nobody before has suggested it could be used to treat cancer.

If San-Millan’s program is anything like the advice handed out after a strenuous workout, it could include hydrating with plenty of water, light stretches and taking magnesium.

He’s also researching compounds that can block lactate from leaving the cell. “When lactate is produced, it has to leave the cell through a transporter. We are trying to block the transporter as well as lactate production inside the cancer cell with different compounds.

“If you block the door, the lactate cannot leave, and the cancer cell will burst,” he explained.

Dr Cantley’s approach is less esoteric: eat less sugar, or, in his case, none at all. “I have a very simple rule. I eat fruit but I don’t eat anything that has sugar added to it. And I guarantee everybody would be better off if they ate zero sugar,” he says.5

He points to reports from the World Health Organization that the average American consumes 126 grams of sugar a day, which is four times the recommended amount the body needs.

“If I say to someone ‘Don’t eat anything sweet for two days,’ they’ll look at me like, ‘That’s impossible, nobody can do that.’ It’s very much like an opioid addiction or an addiction to nicotine.”

Cancer rates have been steadily increasing over the past hundred years. Some of this can be laid at the door of environmental factors such as smoking and pollutants, while the most-cited reason is simply that we’re living longer, and cancer is a disease of old age. But the increase also coincides with the rise of fast-food processing, which uses an abundance of sugars.

This recent surge of interest in his theory came too late for
Warburg, who died in 1970. He was convinced to the end that he had discovered the cause of most cancers, and that future generations would recognize his discoveries. As a reassurance, he had a framed quote from quantum physicist Max Planck that he kept above his desk: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die.”

Stopping the Warburg effect

References
1 Sci Rep, 2018; 8: 8323

Main Article

References
1 Cell, 1987; 50: 1021-9
2 Front Oncol, 2019; 9: 15363. Cancer Cell, 2014; 26: 851-62
3 Ann Transl Med, 2019; 7: 2205. MedicalXpress, March 20, 2019

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