Cancer is the second leading cause of death worldwide, causing more than 10 million deaths annually.
Yet many cancers are curable if caught early and treated effectively. The problem is often the insidiousness of cancer.
A new study reveals there may be a way to identify cancer’s “fingerprints” at the atomic level, using a technique more commonly used in geology than medicine.
This finding may offer new ways to study the growth of cancers in general and may offer new opportunities for early detection.
“This study adds a whole new layer to medicine by allowing us to look at cancer at the atomic level,” said lead author Ashley Maloney, a biogeochemist at the University of Colorado Boulder.
To do this, Maloney and her colleagues from the US and Switzerland took advantage of natural variations in the distribution of hydrogen isotopes – different versions of the same element whose atoms have the same total number of protons but different numbers of neutrons.
Deuterium is the heavier of the two stable isotopes of hydrogen, distinguished from conventional hydrogen by its extra neutron. It is less abundant on Earth, where hydrogen atoms outnumber deuterium by approximately 6,000 to one.
The distribution of these isotopes is useful in the Earth sciences because it holds secrets about things like ancient rocks or ice sheets.
But different arrays of hydrogen atoms also exist within us, and Maloney wanted to see if these isotopes could shed light on the mysteries inside our bodies. Drawing inspiration from her father’s work as a dermatologist, she specifically wanted to learn what hydrogen isotopes could reveal about cancer.
“It takes skin cancer cells from people all the time,” Maloney says. “I wondered how the metabolism of these cells might be different from the cells growing next to them.”
In laboratory experiments, the researchers grew cultures of yeast and mouse liver cells, then analyzed their hydrogen isotopes. They found that cells with very high growth rates – such as cancer cells – have a significantly different ratio of hydrogen to deuterium.
It’s still preliminary, Maloney and her colleagues point out, and many questions remain about how and whether hydrogen isotopes can hint at cancer in the human body.
But given the potential to save lives with earlier detection, it’s worth investigating further, says co-author Sebastian Kopf, a geoscientist at the University of Colorado Boulder.
“Your chances of survival are much higher if you catch cancer early,” Kopf says. “If that isotopic signal is strong enough that you can detect it through something like a blood test, that can give you an important hint that something is wrong.”
Yeast and mouse cells normally generate energy through cellular respiration, taking in oxygen and releasing carbon dioxide. But when oxygen is not freely available, most cells can at least temporarily switch to fermentation to break down sugars into energy.
“In humans, if an athlete performs beyond their aerobic limits, their muscles will also start to ferment, which doesn’t use oxygen,” says Kopf. “It gives you a quick boost of energy.”
Many types of cancer also fuel their growth with fermentation, part of the Warburg effect. Knowing this, scientists have long sought methods to monitor metabolic abnormalities that could herald cancer cells in patients.
In the new study, Maloney and her colleagues tried to track these metabolic changes by analyzing hydrogen isotopes.
Cells obtain hydrogen atoms from an enzyme called nicotinamide adenine dinucleotide phosphate (NADPH). It wears many hats, but one of NADPH’s duties involves allocating hydrogen atoms to certain molecules as part of fatty acid production.
Based on the activity of other enzymes in the cell, NADPH can combine different ratios of hydrogen and deuterium atoms.
Given the tendency of cancer to reconfigure a cell’s metabolism, the researchers hoped to understand whether cancer also changes the way cells obtain hydrogen, thereby affecting their atomic composition.
Their experiments involved colonies of yeast, which often serve as models for studying cancer, as well as colonies of healthy and cancerous mouse liver cells.
The researchers took fatty acid samples from these colonies, then used a mass spectrometer to reveal the ratio of hydrogen isotopes in each sample.
“When we started the study, I thought, ‘Oh, we have a chance to see something cool,'” says Maloney. “It ended up creating a huge signal that I wasn’t expecting.”
Fermenting yeast cells (replacing cancer cells) had about 50 percent fewer deuterium atoms than normal yeast cells, the study found. Mouse cancer cells show a similar but less pronounced decline in deuterium.
“Cancer and other diseases, unfortunately, are a huge topic in many people’s lives. Seeing Ashley’s data was a special, profound moment,” says co-author Xining Zhang, an environmental microbiologist at Princeton University.
“This meant that a tool used to track the health of the planet could also be applied to track health and disease in life forms, hopefully one day in humans.” Growing up in a family challenged by cancer, I hope to see this field expand.”
The study was published in Proceedings of the National Academy of Sciences.
