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Publication Number
US-12306174-B2
Publication Date
2025-05-20
Expiration Date
Abstract
A method for the early detection and monitoring of the progression of cancer by detecting breath biomarkers is provided. The method comprises assessing the activity of an aldo-keto reductase by measuring the concentration of an exogenous substrate for said enzyme and/or measuring the concentration of a metabolite of said substrate in exhaled breath of a subject. Preferably, the cancer is lung cancer.
Core Innovation
The invention relates to a non-invasive method for the detection or prognosis of cancer by assessing the activity of an aldo-keto reductase (AKR). The method is performed by measuring the concentration of an exogenous substrate for the AKR and/or measuring the concentration of a metabolite of the substrate in exhaled breath of a subject. The cancer is lung cancer, and the AKR is AKR1B10 or AKR1B15.
The disclosure frames this as using breath biomarkers based on biotransformation, where the substrate is processed by a cancer-specific AKR and produces measurable substrate/metabolite signals in exhaled breath. The concepts described include substrate washout and/or metabolite accumulation in exhaled breath as measurement notions linked to AKR activity.
The disclosure further describes method variants directed to detection or prognosis, progression monitoring, treatment efficacy, and treatment selection. It also describes embodiments involving volatile organic compound (VOC) substrates, including compounds that may be VOCs such as cinnamaldehyde and cinnamyl alcohol, and optional isotope labeling of a substrate. The described approach can include baseline or reference comparison and risk scoring based on comparisons between a test subject value and reference values.
Claims Coverage
The document contains one independent claim directed to lung cancer detection or prognosis by breath-based assessment of AKR activity using exogenous substrate and/or substrate metabolite concentrations. The claim explicitly includes two AKR targets, AKR1B10 and AKR1B15, and breath-based measurement of substrate and/or metabolite concentrations. Dependent claims refine the measurement context, substrate or metabolite characteristics, isotopic labeling, multi-analyte assessment, and comparison to reference values.
Breath-based AKR activity assessment for lung cancer detection or prognosis
A method for the detection or prognosis of cancer comprising assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of a subject.
AKR1B10 or AKR1B15 specificity for lung cancer
where the cancer is lung cancer and where said AKR is AKR1B10 or AKR1B15.
Volatile organic compound substrate or metabolite measurement
wherein the substrate and/or said metabolite is a volatile organic compound (VOC).
Labelled retinaldehyde substrate
wherein the substrate is labelled retinaldehyde.
Isotope label selection for labelled retinaldehyde
wherein the label is selected from 12C, 13C, 14C, 2H, 14N, or 18O.
Multiple exogenous substrates and/or metabolites
The method further measures the concentration of more than one exogenous substrate and/or more than one metabolite.
Comparison of test subject value to reference values indicating likelihood of cancer
The method compares a test subject value to one or more reference values, where the difference indicates a likelihood of cancer.
Overall claim coverage centers on detecting or providing prognosis for lung cancer by measuring breath concentrations tied to AKR activity, specifically AKR1B10 or AKR1B15. The refinements include VOC substrates, an example labelled retinaldehyde substrate with specified isotopic labels, measurement of more than one substrate and/or metabolite, and using differences versus reference values to indicate likelihood of cancer.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Non-invasive cancer diagnosis and monitoring using breath biomarkers produced by biotransformation of an exogenous substrate by a cancer-specific AKR.
Lung cancer detection or prognosis using measurements of exhaled breath substrate and/or metabolite concentrations linked to AKR1B10 or AKR1B15 activity.
Progression monitoring.
Assessment of treatment efficacy.
Treatment selection.
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