Page 8 Evolution trial: Proof-of-mechanism for a diagnostic probe using an on-breath volatile reporter for lung cancer Dr Mariana Ferreira Leal Owlstone Medical Analysis of volatile metabolites in breath represents an attractive non-invasive diagnostic modality, and potential screening tool, for lung cancer. One of the key challenges is the optimization of the signal-tonoise ratio in a complex matrix as breath. Exogenous Volatile Organic Compound (EVOC®)-probes can be used to detect a cancer-associated enzyme activity and therefore utilised to generate sensitive and specific on-breath signals for lung cancer.We ran a proof-of-mechanism study to evaluate whether administration of D5-ethyl-β-D-glucuronide EVOC-probe specific to tumor-associated extracellular β-glucuronidase results in the production of a unique marker on breath. For this, we first demonstrate that β-glucuronidase is present in the lung cancer microenvironment independent of the tumor stage or histological subtype and therefore an attractive target for a lung cancer diagnostic test. In vitro, we confirmed the probe cleavage by β-glucuronidase. In humans, the administration of the EVOC-probe demonstrated an excellent safety and tolerability profile and D5-ethanol was detected on breath of a subset of individuals after intravenous probe administration.This study provides a proof of mechanism for the cleavage of D5-ethyl-β-D-glucuronide in humans and lay the foundation of a follow-up study to evaluate the diagnostic performance of this breath test for early detection of lung cancer. Dr Mariana Ferreira Leal is a Lead Translational Scientist – Team Lead at Owlstone Medical. At the beginning of her career, she focused on the investigation of gastric cancer diagnostic and prognostic biomarkers. She led her own projects and team before moving to The Institute of Cancer Research in London, where she became interested in the investigation of biomarkers of response to hormone therapies given to breast cancer patients as well as the investigation of mechanism of action and resistance to several compounds in breast cancer models. This knowledge brought her to work in a drug discovery biotech focusing on the modulation of transcription factors in breast cancer. At Owlstone Medical, Dr Mariana Ferreira Leal is focused on the discovery and development of non-invasive tests for lung cancer diagnosis and/or screening based on Breath Biopsy.
RkJQdWJsaXNoZXIy NDMyMTY=