| Title: | Induced-volatolomics for the design of tumour activated therapy |
| Author(s): | Chatre R; Blochouse E; Eid R; Djago F; Lange J; Tarighi M; Renoux B; Sobilo J; Le Pape A; Clarhaut J; Geffroy C; Opalinski I; Tuo W; Papot S; Poinot P; |
| Address: | "University of Poitiers, UMR CNRS 7285, Institut de Chimie des Milieux et Materiaux de Poitiers (IC2MP), Equipe Labellisee Ligue Contre le Cancer 4 Rue Michel-Brunet, TSA 51106 86073 Poitiers Cedex 9 France pauline.poinot@univ-poitiers.fr sebastien.papot@univ-poitiers.fr. UAR No. 44 PHENOMIN TAAM-Imagerie In Vivo, CNRS 3B Rue de la Ferollerie F-45071 Orleans France. CHU de Poitiers 2 Rue de la Mileterie, CS 90577 F-86021 Poitiers France. Seekyo SA 2 Avenue Galilee, BP 30153 86961 Futuroscope France" |
| ISSN/ISBN: | 2041-6520 (Print) 2041-6539 (Electronic) 2041-6520 (Linking) |
| 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 compound (VOC)-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" |
| Notes: | "PubMed-not-MEDLINEChatre, Remi Blochouse, Estelle Eid, Rony Djago, Fabiola Lange, Justin Tarighi, Mehrad Renoux, Brigitte Sobilo, Julien Le Pape, Alain Clarhaut, Jonathan Geffroy, Claude Opalinski, Isabelle Tuo, Wei Papot, Sebastien Poinot, Pauline eng England 2023/05/14 Chem Sci. 2023 Apr 11; 14(18):4697-4703. doi: 10.1039/d2sc06797h. eCollection 2023 May 10" |
