Induced-volatolomics for the design of tumour activated therapy

Abstract

The discovery of tumour-associated markers is of major interest for the development of selective cancer chemotherapy. Within this framework, we introduced the concept of induced-volatolomics enabling to monitor simultaneously the dysregulation of several tumour-associated enzymes in living mice or biopsies. This approach relies on the use of a cocktail of volatile organic compounds (VOCs)-based probes that are activated enzymatically for releasing the corresponding VOCs. Exogenous VOCs can then be detected in the breath of mice or in the headspace above solid biopsies as specific tracers of enzyme activities. Our induced-volatolomics modality highlighted that the up-regulation of N-acetylglucosaminidase was a hallmark of several solid tumours. Having identified this glycosidase as a potential target for cancer therapy, we designed an enzyme-responsive albumin-binding prodrug of the potent monomethyl auristatin E programmed for the selective release of the drug in the tumour microenvironment. This tumour activated therapy produced a remarkable therapeutic efficacy on orthotopic triple-negative mammary xenografts in mice, leading to the disappearance of tumours in 66 % of treated animals. Thus, this study shows the potential of induced-volatolomics for the exploration of biological processes as well as the discovery of novel therapeutic strategies.

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BibTeX RIS

BibTeX

@article{chatre2026inducedvolatolomics,
  title = {{Induced-volatolomics for the design of tumour activated therapy}},
  author = {Rémi Châtre and Estelle Blochouse and Rony Eid and Fabiola Djago and Justin Lange and Mehrad Tarighi and Brigitte Renoux and Julien Sobilo and Alain Le Pape and Jonathan Clarhaut and Claude Geffroy and Isabelle Opalinski and Wei Tuo and Sébastien Papot and Pauline Poinot},
  journal = {Chemical Science},
  year = {2026},
  month = oct,
  doi = {10.1039/d2sc06797h},
  url = {https://hal.science/hal-05777353v1},
  note = {CC BY},
}

RIS

TY  - JOUR
TI  - Induced-volatolomics for the design of tumour activated therapy
AU  - Rémi Châtre
AU  - Estelle Blochouse
AU  - Rony Eid
AU  - Fabiola Djago
AU  - Justin Lange
AU  - Mehrad Tarighi
AU  - Brigitte Renoux
AU  - Julien Sobilo
AU  - Alain Le Pape
AU  - Jonathan Clarhaut
AU  - Claude Geffroy
AU  - Isabelle Opalinski
AU  - Wei Tuo
AU  - Sébastien Papot
AU  - Pauline Poinot
PY  - 2026
DA  - 2026/10/04
JO  - Chemical Science
DO  - 10.1039/d2sc06797h
UR  - https://hal.science/hal-05777353v1
AB  - The discovery of tumour-associated markers is of major interest for the development of selective cancer chemotherapy. Within this framework, we introduced the concept of induced-volatolomics enabling to monitor simultaneously the dysregulation of several tumour-associated enzymes in living mice or biopsies. This approach relies on the use of a cocktail of volatile organic compounds (VOCs)-based probes that are activated enzymatically for releasing the corresponding VOCs. Exogenous VOCs can then be detected in the breath of mice or in the headspace above solid biopsies as specific tracers of enzyme activities. Our induced-volatolomics modality highlighted that the up-regulation of N-acetylglucosaminidase was a hallmark of several solid tumours. Having identified this glycosidase as a potential target for cancer therapy, we designed an enzyme-responsive albumin-binding prodrug of the potent monomethyl auristatin E programmed for the selective release of the drug in the tumour microenvironment. This tumour activated therapy produced a remarkable therapeutic efficacy on orthotopic triple-negative mammary xenografts in mice, leading to the disappearance of tumours in 66 % of treated animals. Thus, this study shows the potential of induced-volatolomics for the exploration of biological processes as well as the discovery of novel therapeutic strategies.
SN  - 2041-6520
SN  - 2041-6539
ER  -

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