Volatilomic response to targeted cancer therapy in vitro

Abstract Clinical advancement of novel therapeutics is often hindered by variable patient responses. Therefore, clinically translatable biomarkers of response are urgently required to facilitate precision medicine trials. Endogenous volatile organic compounds (VOCs) can be non-invasively detected in...

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Main Authors: Philip K. H. Leung, Innah Kim, Bibek Das, George B. Hanna
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04886-5
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author Philip K. H. Leung
Innah Kim
Bibek Das
George B. Hanna
author_facet Philip K. H. Leung
Innah Kim
Bibek Das
George B. Hanna
author_sort Philip K. H. Leung
collection DOAJ
description Abstract Clinical advancement of novel therapeutics is often hindered by variable patient responses. Therefore, clinically translatable biomarkers of response are urgently required to facilitate precision medicine trials. Endogenous volatile organic compounds (VOCs) can be non-invasively detected in exhaled breath and biofluids and have shown great potential for early cancer detection. Since emerging evidence suggests that cancer-associated VOCs may reflect alterations in the tumour lipidome, we speculated that the response to metabolically active therapies could be monitored through VOC measurement. In this proof-of-concept study, we investigated the lipidomic and volatilomic profiles of mTOR catalytic inhibitors (mTORci)-resistant and -sensitive colorectal cancer cells. Distinct lipid-derived VOC signatures, including upregulated alkenes, aldehydes, and fatty acids were observed in mTORci-resistant cells. These enriched VOCs correlated with phospholipid structure and desaturation positions, suggesting that they may be surrogates of dysregulated lipid metabolism. This novel association between VOCs and drug response establishes a precedent for further investigation into VOC biomarkers of treatment response. VOCs associated with therapy response in vitro need to be targeted in clinical trials to identify biomarkers that could be translated to monitor therapeutic response in a clinical setting.
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spelling doaj-art-c564b9b67d5a443fb154b50cdb1fdea62025-08-24T11:23:45ZengNature PortfolioScientific Reports2045-23222025-06-0115111010.1038/s41598-025-04886-5Volatilomic response to targeted cancer therapy in vitroPhilip K. H. Leung0Innah Kim1Bibek Das2George B. Hanna3Division of Surgery, Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalDivision of Surgery, Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalDivision of Surgery, Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalDivision of Surgery, Department of Surgery and Cancer, Imperial College London, Hammersmith HospitalAbstract Clinical advancement of novel therapeutics is often hindered by variable patient responses. Therefore, clinically translatable biomarkers of response are urgently required to facilitate precision medicine trials. Endogenous volatile organic compounds (VOCs) can be non-invasively detected in exhaled breath and biofluids and have shown great potential for early cancer detection. Since emerging evidence suggests that cancer-associated VOCs may reflect alterations in the tumour lipidome, we speculated that the response to metabolically active therapies could be monitored through VOC measurement. In this proof-of-concept study, we investigated the lipidomic and volatilomic profiles of mTOR catalytic inhibitors (mTORci)-resistant and -sensitive colorectal cancer cells. Distinct lipid-derived VOC signatures, including upregulated alkenes, aldehydes, and fatty acids were observed in mTORci-resistant cells. These enriched VOCs correlated with phospholipid structure and desaturation positions, suggesting that they may be surrogates of dysregulated lipid metabolism. This novel association between VOCs and drug response establishes a precedent for further investigation into VOC biomarkers of treatment response. VOCs associated with therapy response in vitro need to be targeted in clinical trials to identify biomarkers that could be translated to monitor therapeutic response in a clinical setting.https://doi.org/10.1038/s41598-025-04886-5Volatile organic compoundsGas chromatography-mass spectrometryLipid peroxidationMulti-omicsGastrointestinal cancersColorectal cancer
spellingShingle Philip K. H. Leung
Innah Kim
Bibek Das
George B. Hanna
Volatilomic response to targeted cancer therapy in vitro
Scientific Reports
Volatile organic compounds
Gas chromatography-mass spectrometry
Lipid peroxidation
Multi-omics
Gastrointestinal cancers
Colorectal cancer
title Volatilomic response to targeted cancer therapy in vitro
title_full Volatilomic response to targeted cancer therapy in vitro
title_fullStr Volatilomic response to targeted cancer therapy in vitro
title_full_unstemmed Volatilomic response to targeted cancer therapy in vitro
title_short Volatilomic response to targeted cancer therapy in vitro
title_sort volatilomic response to targeted cancer therapy in vitro
topic Volatile organic compounds
Gas chromatography-mass spectrometry
Lipid peroxidation
Multi-omics
Gastrointestinal cancers
Colorectal cancer
url https://doi.org/10.1038/s41598-025-04886-5
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AT innahkim volatilomicresponsetotargetedcancertherapyinvitro
AT bibekdas volatilomicresponsetotargetedcancertherapyinvitro
AT georgebhanna volatilomicresponsetotargetedcancertherapyinvitro