Fasting-mimicking diet and hormone therapy induce breast cancer regression

Irene Caffa, Vanessa Spagnolo, Claudio Vernieri, Francesca Valdemarin, Pamela Becherini, Min Wei, Sebastian Brandhorst, Chiara Zucal, Else Driehuis, Lorenzo Ferrando, Francesco Piacente, Alberto Tagliafico, Michele Cilli, Luca Mastracci, Valerio G. Vellone, Silvano Piazza, Anna Laura Cremonini, Raffaella Gradaschi, Carolina Mantero, Mario Passalacqua, Alberto Ballestrero, Gabriele Zoppoli, Michele Cea, Annalisa Arrighi, Patrizio Odetti, Fiammetta Monacelli, Giulia Salvadori, Salvatore Cortellino, Hans Clevers, Filippo Braud, Samir G. Sukkar, Alessandro Provenzani, Valter D. Longo () and Alessio Nencioni ()
Additional contact information
Irene Caffa: IRCCS Ospedale Policlinico San Martino
Vanessa Spagnolo: University of Milan
Claudio Vernieri: IFOM, FIRC Institute of Molecular Oncology
Francesca Valdemarin: IRCCS Ospedale Policlinico San Martino
Pamela Becherini: IRCCS Ospedale Policlinico San Martino
Min Wei: University of Southern California
Sebastian Brandhorst: University of Southern California
Chiara Zucal: University of Trento
Else Driehuis: Royal Netherlands Academy of Arts and Sciences
Lorenzo Ferrando: University of Genoa
Francesco Piacente: IRCCS Ospedale Policlinico San Martino
Alberto Tagliafico: University of Genoa
Michele Cilli: IRCCS Ospedale Policlinico San Martino
Luca Mastracci: IRCCS Ospedale Policlinico San Martino
Valerio G. Vellone: IRCCS Ospedale Policlinico San Martino
Silvano Piazza: University of Trento
Anna Laura Cremonini: IRCCS Ospedale Policlinico San Martino
Raffaella Gradaschi: IRCCS Ospedale Policlinico San Martino
Carolina Mantero: IRCCS Ospedale Policlinico San Martino
Mario Passalacqua: University of Genoa
Alberto Ballestrero: IRCCS Ospedale Policlinico San Martino
Gabriele Zoppoli: IRCCS Ospedale Policlinico San Martino
Michele Cea: IRCCS Ospedale Policlinico San Martino
Annalisa Arrighi: University of Genoa
Patrizio Odetti: IRCCS Ospedale Policlinico San Martino
Fiammetta Monacelli: IRCCS Ospedale Policlinico San Martino
Giulia Salvadori: University of Milan
Salvatore Cortellino: IFOM, FIRC Institute of Molecular Oncology
Hans Clevers: Royal Netherlands Academy of Arts and Sciences
Filippo Braud: University of Milan
Samir G. Sukkar: IRCCS Ospedale Policlinico San Martino
Alessandro Provenzani: University of Trento
Valter D. Longo: IFOM, FIRC Institute of Molecular Oncology
Alessio Nencioni: IRCCS Ospedale Policlinico San Martino

Nature, 2020, vol. 583, issue 7817, 620-624

Abstract: Abstract Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3–5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT–mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2502-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7817:d:10.1038_s41586-020-2502-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2502-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().