Alexandra Martin at the Breath Biopsy Conference 2022

[18 mins] Targeting tumour associated aldo-keto reductase with exogenous volatile organic compound (EVOC) Probes using High-Capacity Sorptive Extraction (HiSorb) headspace GCMS to detect lung cancer


00:00 Introduction 

0:43 Talk

12:19 Q&A 

Talk Abstract:

Early detection could improve cancer survival, but this requires effective screening methods. Non-invasive breath tests targeting lung cancer metabolism represent a promising screening option.

Tumor cells adapt to survive. For example, lung cancers cope with oxidative stress by upregulating aldo-keto reductase (AKR) enzymes including AKR1B10 and AKR1B15 that reduce aldehydes into alcohols. We are investigating the possibility of a cancer breath test based on monitoring AKR activity via volatile aldehydes and alcohols.

We measured AKR1B10/B15 activity in vitro in lung cancer cells by administering aldehydes as exogenous volatile organic compound (EVOC) Probes and monitoring alcohol production. To assess relationships between volatiles and AKR metabolism we tested the effect of chemical (tolrestat and JF0064) and biological (CRISPR-cas9 knockout mutants of AKR1B10/B15) AKR inhibitors. To assess evaporation, a parallel experiment analysed the same volatiles in cell culture medium (no cells). Supernatant was collected at several timepoints after the addition of aldehyde probes and analysed using an automated headspace HiSorb extraction platform (Centri) and GC-MS.

Wildtype and vehicle samples showed lower aldehyde and higher alcohol levels compared to evaporation controls, confirming that AKRs are active in these cells. Moreover, as expected, activity was reduced by AKR inhibition. We observed no significant difference in aldehyde abundance but did see reduced production of alcohols in cells with inhibited AKR activity.

We demonstrate that alcohol/aldehyde ratio reflects AKR activity in cancer cells treated with aldehydes as EVOC Probes and that the same approach may be suitable for lung cancer detection on breath.

Speaker Biography:

Following her MSci in Natural Sciences at the University of Birmingham, Alexandra completed her PhD in Biophysical Chemistry at the University of Birmingham in 2020, researching the physicochemical differences between mammalian and bacterial model cell membranes. She joined Owlstone in 2020 as an Applications Chemist and works on Breath Biopsy test projects aiming to diagnose early-stage lung cancer and other diseases using breath sampling. Alexandra leads analytical development using in vitro headspace GC-MS techniques at Owlstone to screen biomarkers and target metabolic pathways, and find novel markers.

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