Volatilomic response to targeted cancer therapy in vitro
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Published version
Author(s)
Leung, Kwan Hung Philip
Kim, Innah
Das, Bibek
Hanna, George
Type
Journal Article
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.
Date Issued
2025-06-03
Date Acceptance
2025-05-29
Citation
Scientific Reports, 2025, 15
ISSN
2045-2322
Publisher
Nature Portfolio
Journal / Book Title
Scientific Reports
Volume
15
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41598-025-04886-5
Subjects
Volatile organic compounds
Gas chromatography-mass spectrometry
Lipid peroxidation
Multiomics
Gastrointestinal cancers
Colorectal cancer
Publication Status
Published
Article Number
19445
Date Publish Online
2025-06-03