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Cancer cells and non-cancer cells differ in metabolism and emit distinct volatile compounds, allowing them to be distinguished by their scent. Insect odorant receptors are excellent chemosensors with high sensitivity and a broad receptive range. Putting these two ideas together, collaborating scientists from University of Konstanz (Germany) and University of Rome (Italy) investigated the potential of using the fruit fly's olfactory system to detect cancer cells. In previous work, dogs have been used for cancer chemosensing, but although their olfaction may be sensitive and accurate, the approach has the limitation that its 'readout' is only indirect, based on the animal's behavior in combination with a human trainer and interpreter. This limitation means that results of chemosensing experiments using dogs are difficult to quantify and therefore can't be reliably used in clinical diagnostics. In contrast, the new fruit fly system avoids a behavioral readout and instead uses a direct readout of the insect's antenna responses obtained by calcium imaging. “What really is new and spectacular about this result is the combination of objective, specific and quantifiable laboratory results and the extremely high sensitivity of a living being that cannot be matched by electronic noses or gas chromatography,” explained Giovanni Galizia, leader of the project, in a press release.

In fruit fly antennae, single odorant molecules dock to receptor neurons, activating them. The scientists used calcium imaging to record the pattern of neuron activation in response to scent samples from cultures of cancer cells, cultures of healthy cells or culture medium. The response patterns were different for cancerous versus healthy cells and were conserved among individual flies. Therefore, the response patterns could be used to distinguish samples of healthy cells from those of cancerous cells and even to distinguish two different groups of cancer samples according to their proliferation rates (Sci. Rep. 4, 3576; 2014).

The results serve as proof of the concept that the fruit fly olfactory system can detect and discriminate among medically relevant odors at low concentrations and is therefore suitable for medical applications. “The high sensitivity of the natural olfactory receptors, paired with the quickness with which we can generate these test results, might lead to the development of a cheap, fast and highly efficient pre-screening that can detect cancer cells well before we can discover them with the present diagnostic imaging techniques,” noted Galizia. In the future, the scientists plan to work on integrating the odorant receptors into artificial systems with the potential for real-time readouts.