Dynamic volatolomic profiling reveals treatment-induced metabolic state transitions during radiosensitization in colorectal cancer
Abstract
Radiotherapy resistance remains a major challenge in colorectal cancer (CRC), necessitating strategies that not only enhance radiosensitivity but also enable real-time monitoring of treatment-associated biological responses. Here, we present an integrated systems-level framework combining network pharmacology, in silico target analysis, in vitro validation, and dynamic volatolomic profiling to investigate metabolic adaptations associated with curcumin-mediated radiosensitization. Network-based analyses identified curcumin as a multi-target modulator of key radiation-response pathways, including PI3K/Akt, EGFR, STAT3, and apoptosis-related signaling. Functional validation in Caco-2 cells demonstrated enhanced radiosensitivity following curcumin treatment, evidenced by increased radiation-induced cytotoxicity and apoptosis, together with reduced clonogenic survival and migratory capacity. Dynamic volatolomic profiling using an electronic nose (eNose) revealed that treatment-associated metabolic changes could be continuously monitored through volatile organic compound (VOC) emissions. Time-resolved trajectory analysis, vector-field modeling, Hidden Markov Model state inference, and Markov transition analysis demonstrated that VOC signatures encode dynamic metabolic-state evolution and probabilistic state transitions during treatment response. Curcumin reduced baseline VOC emissions, whereas irradiation induced dose-dependent metabolic perturbations associated with nonlinear VOC trajectories. Combined treatment generated distinct state-dependent VOC signatures consistent with enhanced metabolic reprogramming during radiosensitization. By integrating molecular signaling, cellular phenotypes, and dynamic VOC outputs, this study extends volatolomics beyond conventional classification-based applications and establishes a systems-level framework for monitoring treatment-induced metabolic-state transitions. These findings support the potential of eNose-based volatolomics as a non-invasive platform for real-time assessment of radiosensitization and therapeutic response in CRC.
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BibTeX
@article{youssef2026dynamic,
title = {{Dynamic volatolomic profiling reveals treatment-induced metabolic state transitions during radiosensitization in colorectal cancer}},
author = {Omnia G. Youssef and Mohamed S. Mshaly and Mazen S. Soliman and Ashraf K. Awaad and Ehab I. Mohamed},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-72523-w},
url = {https://www.nature.com/articles/s41598-026-72523-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dynamic volatolomic profiling reveals treatment-induced metabolic state transitions during radiosensitization in colorectal cancer
AU - Omnia G. Youssef
AU - Mohamed S. Mshaly
AU - Mazen S. Soliman
AU - Ashraf K. Awaad
AU - Ehab I. Mohamed
PY - 2026
DA - 2026/10/20
JO - Scientific Reports
DO - 10.1038/s41598-026-72523-w
UR - https://www.nature.com/articles/s41598-026-72523-w
AB - Radiotherapy resistance remains a major challenge in colorectal cancer (CRC), necessitating strategies that not only enhance radiosensitivity but also enable real-time monitoring of treatment-associated biological responses. Here, we present an integrated systems-level framework combining network pharmacology, in silico target analysis, in vitro validation, and dynamic volatolomic profiling to investigate metabolic adaptations associated with curcumin-mediated radiosensitization. Network-based analyses identified curcumin as a multi-target modulator of key radiation-response pathways, including PI3K/Akt, EGFR, STAT3, and apoptosis-related signaling. Functional validation in Caco-2 cells demonstrated enhanced radiosensitivity following curcumin treatment, evidenced by increased radiation-induced cytotoxicity and apoptosis, together with reduced clonogenic survival and migratory capacity. Dynamic volatolomic profiling using an electronic nose (eNose) revealed that treatment-associated metabolic changes could be continuously monitored through volatile organic compound (VOC) emissions. Time-resolved trajectory analysis, vector-field modeling, Hidden Markov Model state inference, and Markov transition analysis demonstrated that VOC signatures encode dynamic metabolic-state evolution and probabilistic state transitions during treatment response. Curcumin reduced baseline VOC emissions, whereas irradiation induced dose-dependent metabolic perturbations associated with nonlinear VOC trajectories. Combined treatment generated distinct state-dependent VOC signatures consistent with enhanced metabolic reprogramming during radiosensitization. By integrating molecular signaling, cellular phenotypes, and dynamic VOC outputs, this study extends volatolomics beyond conventional classification-based applications and establishes a systems-level framework for monitoring treatment-induced metabolic-state transitions. These findings support the potential of eNose-based volatolomics as a non-invasive platform for real-time assessment of radiosensitization and therapeutic response in CRC.
SN - 2045-2322
ER -