Fiche publication
Date publication
octobre 2017
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MERLIN Jean-Louis
,
Dr RIOS Maria
Tous les auteurs :
Jobard E, Trédan O, Bachelot T, Vigneron AM, Aït-Oukhatar CM, Arnedos M, Rios M, Bonneterre J, Diéras V, Jimenez M, Merlin JL, Campone M, Elena-Herrmann B
Lien Pubmed
Résumé
The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2. Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E). Longitudinal series of NMR serum metabolic profiles were exploited to investigate treatment effects on the patients metabolism over time, in both group. Trastuzumab and everolimus combination induces faster changes in patients metabolism than trastuzumab alone, visible after only one week of treatment as well as a residual effect detectable up to three weeks after ending the treatment. These metabolic fingerprints highlight the involvement of several metabolic pathways reflecting a systemic effect, particularly on the liver and visceral fat. Comparison of serum metabolic profiles between the two arms shows that everolimus, an mTORC1 inhibitor, is responsible for host metabolism modifications observed in arm T+E. In HER-2 positive breast cancer, our metabolomic approach confirms a fast and persistent host metabolism modification caused by mTOR inhibition.
Mots clés
HER-2 positive breast cancer, mTOR inhibitor, metabolomics, nuclear magnetic resonance, targeted therapies
Référence
Oncotarget. 2017 Oct 13;8(48):83570-83584