What does cancer smell like?

UEF Bulletin 2016

In the future, cancer may be diagnosed by its smell, and polyamines may be the key to new diagnostics.

Many studies have concluded that cancer has a distinct smell. Dogs can be trained and electronic noses programmed to recognise cancer by smelling patient samples, but there is still no certainty about what exactly causes the smell.

According to Professor Jouko Vepsäläinen (in the photo above), the answer may be polyamines. They are a group of molecules that play an important role in cell growth, proliferation and differentiation. Increased cell proliferation and raised polyamine levels are typical in cancer. What’s more, polyamines actually smell bad.

Vepsäläinen has been studying the role of polyamines in cancer for almost 20 years with other UEF pioneers in the field, Professor Leena Alhonen and the late Professor Juhani Jänne. More recently, and with the university's strategic funding, his Wet Chemistry Alliance group at the School of Pharmacy has joined forces with researchers in Tampere and Helsinki to develop cancer diagnostics possibly based on patients’ polyamine profiles. To better understand the function and potential of polyamines, his group develops the analytics and synthesis of polyamines and searches for new therapeutic purposes for drugs affecting polyamine metabolism.

The smell of cancer is caused by a mixture of volatile compounds, which are laborious and costly to identify with traditional analytics. Vepsäläinen's group has developed a quicker method based on liquid chromatography and tandem mass spectrometry (LC-MS/MS), with which a variety of polyamines can be analysed simultaneously.

Urine samples are measured by LC-MS/MS using specific ions for each polyamine, visualised as peaks in the chromatogram.

Besides all polyamines common in human cells, the group was the first in the world to synthesise their deuterium-labelled counterparts, which are used as internal standards in the analysis, necessary for accurate quantitative polyamine profiling and thus detecting cancer from patients’ urine samples.

“We have been able to discriminate prostate cancer from benign prostatic enlargement, to detect ovarian cancer and to tell which stage the cancer is in, based on polyamine profiles,” Vepsäläinen says.

” Next, we plan to analyze samples from other common cancers.”

Applying the results to an electronic nose, Dr Niku Oksala's group at the University of Tampere was able to detect prostate cancer from urine smell print profiles just as well as the common PSA test from blood.

“Our analytics are not feasible for clinical use yet, but a portable eNose has wide potential in the screening, diagnostics and follow-up of cancer. It could enable earlier diagnostics and thus a better outcome of many cancers, and reduce the need for expensive tests and biopsies,” Vepsäläinen says.

However, an electronic nose can't recognise individual compounds, just a smell pattern based on provided data. More research is needed to ensure that what it detects are indeed polyamines, and to train it to recognise polyamine profiles in different cancers.

Here dogs come to rescue. In cooperation with Docent Anna Hielm-Björkman's Dogrisk project at the University of Helsinki, dogs trained to detect cancer from urine samples will be given samples with synthesised polyamines imitating cancerous polyamine profiles. “If the dogs pick these samples, we can be quite sure that polyamines cause the smell.”

Her focus on dogs, Hielm-Björkman reveals that dogs' cancer samples have an added benefit in research. - Food contains polyamines as well, but with dogs it's easy to eliminate the impact of different food products on polyamine levels by keeping them all on a similar diet.

The development of polyamine analytics as well as the extensive synthesis and deuterium-labelling of polyamines on Kuopio Campus is much the result of Dr. Merja Häkkinen's several years' work. The research group has already received inquiries from international pharmaceutical stakeholders willing to buy the molecules for their own research use.

Häkkinen points outs that polyamines can be important markers not just in diagnostics, but in assessing patients' response to treatment. - In the samples we have analyzed, cancer patients' polyamine profiles have differed before and after surgery.

The applications of polyamine profiling range from different types of cancer to many other diseases where altered polyamine levels have been observed, such as urinary tract infections. They are common among aged population, and in older people they may cause behavioural symptoms that can be confused with symptoms of dementia.

- A few years from now, urinary tract infections may be diagnosed in a matter of minutes at the patient's home using an electronic nose, predicts Docent Tuomo Keinänen who also works in Vepsäläinen's group.

Besides health care, polyamine measurements can benefit the food industry. - For example, in live fish transport tanks, small alterations in polyamine levels could help detect dead fish that would otherwise contaminate the whole lot, Keinänen says.

- Polyamine metabolism as a drug treatment target is another area of research where a lot is happening at the moment. Many drugs that are in clinical use for other purposes have an impact of polyamine functions, which may make them useful in the treatment of cancer or other diseases they were not originally aimed at.

For example, the group has ifentified a polyamine target for metformin, a diabetes drug now showing anti-cancer potential. - It takes a lot of time and money to develop entirely new drugs, whereas it's much faster and cheaper to look for new purposes for tried and tested drugs that are already on the market.

Text: Ulla Kaltiala Photos: Raija Törrönen