@article {44689,
	title = {Short term starvation potentiates the efficacy of chemotherapy in triple negative breast cancer via metabolic reprogramming},
	journal = {Journal of Translational Medicine},
	volume = {21},
	number = {1},
	year = {2023},
	note = {Pateras, Ioannis SWilliams, ChloeGianniou, Despoina DMargetis, Aggelos TAvgeris, MargaritisRousakis, PantelisLegaki, Aigli-IoannaMirtschink, PeterZhang, WeiPanoutsopoulou, KonstantinaDelis, Anastasios DPagakis, Stamatis NTang, WeiAmbs, StefanWarpman Berglund, UlrikaHelleday, ThomasVarvarigou, AnastasiaChatzigeorgiou, AntoniosNordstrom, AndersTsitsilonis, Ourania ETrougakos, Ioannis PGilthorpe, Jonathan DFrisan, TeresaengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2023/03/04 06:00J Transl Med. 2023 Mar 3;21(1):169. doi: 10.1186/s12967-023-03935-9.},
	month = {Mar 3},
	pages = {169},
	abstract = {BACKGROUND: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized. METHODS: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H(2)DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model. RESULTS: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model. CONCLUSIONS: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.},
	keywords = {*Drug-Related Side Effects and Adverse Reactions, *Triple Negative Breast Neoplasms, Animals, breast cancer, Caloric Restriction, Diet, Reducing, Fasting, Humans, Metabolic reprogramming, Mice, Mitochondria, Obesity, Oncological treatment, Oxidative Stress, Reactive Oxygen Species, Starvation, Triple negative breast cancer},
	isbn = {1479-5876 (Electronic)1479-5876 (Linking)},
	author = {Pateras,I.S. and Williams, C. and Gianniou, D. D. and Margetis, A. T. and Avgeris, M. and Rousakis, P. and Legaki, A. I. and Mirtschink, P. and Zhang, W. and Panoutsopoulou, K. and Delis, A. D. and Pagakis, S. N. and Tang, W. and Ambs, S. and Warpman Berglund, U. and Helleday, T. and Varvarigou, A. and Chatzigeorgiou, A and Nordstrom, A. and Tsitsilonis, O.E. and Trougakos, I.P. and Gilthorpe, J. D. and Frisan, T.}
}
