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Fasting-mimicking diet and hormone therapy induce breast cancer regression

Author

Listed:
  • Irene Caffa

    (IRCCS Ospedale Policlinico San Martino)

  • Vanessa Spagnolo

    (University of Milan
    IFOM, FIRC Institute of Molecular Oncology)

  • Claudio Vernieri

    (IFOM, FIRC Institute of Molecular Oncology
    Fondazione IRCCS Istituto Nazionale dei Tumori)

  • Francesca Valdemarin

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Pamela Becherini

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • 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
    University Medical Center Utrecht)

  • Lorenzo Ferrando

    (University of Genoa)

  • Francesco Piacente

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Alberto Tagliafico

    (University of Genoa)

  • Michele Cilli

    (IRCCS Ospedale Policlinico San Martino)

  • Luca Mastracci

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Valerio G. Vellone

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Silvano Piazza

    (University of Trento)

  • Anna Laura Cremonini

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • 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
    University of Genoa)

  • Gabriele Zoppoli

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Michele Cea

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Annalisa Arrighi

    (University of Genoa)

  • Patrizio Odetti

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Fiammetta Monacelli

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

  • Giulia Salvadori

    (University of Milan
    IFOM, FIRC Institute of Molecular Oncology)

  • Salvatore Cortellino

    (IFOM, FIRC Institute of Molecular Oncology)

  • Hans Clevers

    (Royal Netherlands Academy of Arts and Sciences
    University Medical Center Utrecht
    Princess Maxima Center for Pediatric Oncology)

  • Filippo Braud

    (University of Milan
    Fondazione IRCCS Istituto Nazionale dei Tumori)

  • Samir G. Sukkar

    (IRCCS Ospedale Policlinico San Martino)

  • Alessandro Provenzani

    (University of Trento)

  • Valter D. Longo

    (IFOM, FIRC Institute of Molecular Oncology
    University of Southern California)

  • Alessio Nencioni

    (IRCCS Ospedale Policlinico San Martino
    University of Genoa)

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.

Suggested Citation

  • Irene Caffa & Vanessa Spagnolo & Claudio Vernieri & Francesca Valdemarin & Pamela Becherini & Min Wei & Sebastian Brandhorst & Chiara Zucal & Else Driehuis & Lorenzo Ferrando & Francesco Piacente & Al, 2020. "Fasting-mimicking diet and hormone therapy induce breast cancer regression," Nature, Nature, vol. 583(7817), pages 620-624, July.
  • Handle: RePEc:nat:nature:v:583:y:2020:i:7817:d:10.1038_s41586-020-2502-7
    DOI: 10.1038/s41586-020-2502-7
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    Cited by:

    1. S. Cortellino & V. Quagliariello & G. Delfanti & O. Blaževitš & C. Chiodoni & N. Maurea & A. Mauro & F. Tatangelo & F. Pisati & A. Shmahala & S. Lazzeri & V. Spagnolo & E. Visco & C. Tripodo & G. Caso, 2023. "Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Laura C. D. Pomatto-Watson & Monica Bodogai & Oye Bosompra & Jonathan Kato & Sarah Wong & Melissa Carpenter & Eleonora Duregon & Dolly Chowdhury & Priya Krishna & Sandy Ng & Emeline Ragonnaud & Robert, 2021. "Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    3. Amr Khalifa & Ana Guijarro & Silvia Ravera & Nadia Bertola & Maria Pia Adorni & Bianca Papotti & Lizzia Raffaghello & Roberto Benelli & Pamela Becherini & Asmaa Namatalla & Daniela Verzola & Daniele R, 2023. "Cyclic fasting bolsters cholesterol biosynthesis inhibitors’ anticancer activity," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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