Lung cancer will ‘eat’ almost anything to survive

Lung cancer relies on glucose (sugar) to stay strong and proliferate, but "can use alternative fuel sources to help drive their growth under stressful conditions," says Russell Jones. "This remarkable flexibility is part of what makes cancer so deadly, but offers hope in finding new therapies." (Credit: Jeffrey/Flickr)

Scientists think it’s possible to starve lung cancer by blocking access to other sources of food when sugar is scarce.

The metabolism of cancer cells is very different from normal cells. Rapid proliferation means that cancer cells have increased energetic needs. This need is met using glucose (sugar) as the main source of nutrition.

When sugar is scarce, some lung cancer cells change their food preferences—switching from glucose to the amino acid glutamine.

Cancer cells use glucose at rates tens or even hundreds of times larger than that of normal cells. But, when glucose becomes scarce, they need to get their nutrition from somewhere else to maintain their growth and survival.

For a new study published in the journal Molecular Cell, researchers looked at the response of cancer cells to reduced availability of glucose, the main fuel source for most cancer cells. The group chose to experiment with one of the most common types of lung cancer—non-small cell lung cancer, which affects 85-90 percent of all lung cancer victims. They discovered that when sugar is scarce, some lung cancer cells change their food preferences—switching from glucose to the amino acid glutamine.

Cancer cells use an enzyme called PEPCK to reprogram cancer cell metabolism, says Emma Vincent, research associate at McGill University.

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“Until recently, PEPCK has only been extensively studied in specialized tissues that make glucose, such as the liver. We found that some cancer cells also express PEPCK, and this confers to them the ability to convert glutamine into energy and building blocks to support their growth. By making this metabolic switch, PEPCK allows cancer cells not just to survive, but to continue to proliferate under starvation conditions.”

The scientists demonstrated that blocking PEPCK in cancer cells could slow tumor growth in mice—and also found evidence of increased PEPCK levels in tissues from lung-cancer patients. “The fact that PEPCK levels are elevated in some cases of human lung cancer suggests that this enzyme may play a role in the human disease,” says Russell Jones, associate professor of physiology.

The study suggests that nutrient availability in the organism, where cancer cells must compete for glucose and other nutrients, can impact cancer progression. “Our work shows that cancers can use alternative fuel sources to help drive their growth under stressful conditions,” Jones says. “This remarkable flexibility is part of what makes cancer so deadly, but offers hope in finding new therapies.”

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“Understanding the mechanisms used by cancer cells to adapt to their environment creates new possibilities to treat this deadly disease,” says Alexey Sergushichev, bioinformatician and PhD student in the computer technologies department at ITMO University in Saint Petersburg, Russia. “We hope our work on PEPCK and the metabolic alterations in lung cancer cells will lead to innovations in treatment for non-small cell lung cancer, one of the most deadly types of cancer.”

Researchers from Washington University in St. Louis and the University of Bristol contributed to the study. lntegrated Cancer Research Training Program, the Government of the Russian Federation, the Fonds de recherche Santé Québec, the Wellcome Trust Seeding Drug Discovery Award, the Canadian Institutes of Health Research, the Terry Fox Foundation, and the Cancer Research Society funded the work.

Source: McGill University