Breath-based detection of lung cancer using Exogenous Volatile Organic Compound targeting β-glucuronidase in the tumor microenvironment

Christiaan Frederick Labuschagne 1, Rob Smith 1, Mariana Leal 1, Neelam Kumar 3, Max Allsworth 1, Billy Boyle 1, Philip Crosbie 2, Sam Janes 3, Robert Rintoul 4,5

1. Owlstone Medical Ltd., Cambridge, UK,
2. The University of Manchester, Manchester, UK,
3. University College Hospital, London, UK,
4. Department of Oncology, University of Cambridge, Cambridge, UK,
5. Royal Papworth Hospital, Cambridge, UK,

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Abstract: Lung cancer is a leading cause of death worldwide (1.8 million deaths in 2020). 5-year survival is around 16% and this has not improved over the last 40 years. A key issue is late diagnosis.  

Widespread public screening represents one of the greatest opportunities to improve early detection. However, currently suitable methods are not easily accessible to the majority of the population. A breath test would be more affordable, easy to use and accessible. 

Breath is a complex sampling matrix, with high background signal. One solution to administer a molecular probe (EVOC® Probe) that is responsive to disease-specific metabolic pathways. In 2019, Lange et al. reported the use of D5-ethyl-βD-glucuronide (D5-EthGlu) as probe in mice. This study used animal, in vitro, in vivo and clinical work to assess the viability of D5-EthGlu as a EVOC Probe in human lung cancers. 

In vitro, cells were cultured for 48 hours before supernatant was collected and β-glucuronidase activity was measured. We also xenografted tumors subcutaneously onto mice before administering probes. β-glucuronidase expression in the tumour microenvironment (TME) was observed at all stages of lung cancer including stage 1. There was no extracellular β-glucuronidase expression in healthy tissue. Healthy individuals and 1 lung cancer patient were dosed with the first version of the probe. Very low to no signal was detected in healthy individuals with a higher response in the lung cancer patient.  

Our evidence appears to support the application of D5-EthGlu as an EVOC Probe to enable non-invasive breath testing as a means for early detection of lung cancer via public screening.