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Biomedicine

The Smell of Cancer

Skin-cancer tumors give off a characteristic odor profile that could be used for early detection.

People who are prone to developing skin cancer have to undergo frequent exams and biopsies of suspicious moles in order to catch tumors at an early stage. But a new finding suggests a quicker, noninvasive method for detection. Scientists have identified a characteristic odor profile given off by skin-cancer tumors, which might one day allow diagnosis by a wave of a detector across the skin.

Smelling skin cancer: An alcohol solution is dripped onto a volunteer’s forearm to collect compounds on the skin’s surface. The sample is then analyzed by gas chromatography/mass spectrometry to identify the chemicals present.

In the United States, more than a million skin cancers are diagnosed each year. Basal cell and squamous cell carcinomas are the most common types, although they rarely spread and usually are not fatal. Melanoma, which accounts for less than 5 percent of skin-cancer cases, causes the majority of skin-cancer deaths.

Scientists have long surmised that tumors give off a unique smell, thanks to studies showing that dogs have the ability to sniff out melanomas and other cancers. For example, Armand Cognetta, a dermatologist in Tallahassee, FL, trained a dog to find melanoma samples hidden around a room, as well as detect melanomas on skin-cancer patients. “The dogs were definitely smelling something, and nobody has been able to pinpoint what it could be,” says Michelle Gallagher, formerly a postdoctoral researcher at the Monell Chemical Senses Center, in Philadelphia, and now a senior scientist at Rohm & Haas, a materials company in Spring House, PA.

So Gallagher and her advisor, Monell chemist George Preti, set out to identify the odor markers. Working with dermatologists at the University of Pennsylvania, Gallagher and Preti recruited 11 people with basal cell carcinoma for the study, as well as controls matched for age, gender, and ethnicity. The volunteers went through a weeklong “wash-out” process in which they used fragrance-free shampoo and soap and wore T-shirts provided by the researchers to eliminate odors from external sources.

The researchers then collected odor samples by placing a funnel with an absorbent fiber over the volunteers’ skin for 30 minutes. They also washed the skin with an alcohol solution to collect compounds sitting on the surface. “We found two chemicals in particular that were significantly different when you compared a cancer patient with a healthy subject,” Gallagher says. Both compounds were present in the healthy volunteers, but one compound was at a higher concentration and the other at a lower concentration above the tumors in the cancer patients. The researchers presented their findings at the American Chemical Society meeting in Philadelphia.

The scientists are not sure what biochemical pathway might be generating those two compounds or what process is causing the change in concentration. “It’s not surprising that there might be a physical or chemical basis to this distinctive pattern of odors,” says dermatologist Paul Nghiem of the University of Washington and the Fred Hutchinson Cancer Research Center, in Seattle, who was not involved in the study. Skin-cancer cells act differently on many levels, from gene expression to protein synthesis. “If some of those proteins are volatile, it’s not a stretch” that differences could be detected, Nghiem says.

Gallagher and Preti are continuing to look for other biomarkers for skin cancer. When they’re identified, sensor technology like the electronic noses under development could be programmed with the levels of chemicals indicative of a tumor. “Instead of a visual exam and a biopsy, you could have a sensor that you could wave across the body,” Gallagher says.

The current study focused on patients with basal cell carcinoma because there are many more cases of this cancer than there are of the more serious melanoma, making it easier to recruit volunteers. The researchers are actively looking for patients with melanoma so that they can repeat the study. “We have to have a window where it’s safe for them to be diagnosed and not come back to the doctor for a week or two,” Gallagher says, giving the patients time to do the wash-out and participate in the odor sampling.

It is with melanoma that a rapid detection method would be most useful, says Nghiem. “It’s a life-threatening disease and can be clinically difficult to diagnose,” he says. Basal cell carcinoma, on the other hand, is fairly easy to diagnose, rarely fatal, and readily curable by surgery.

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