2. Academic Validation
  3. Fasting-mimicking diet and hormone therapy induce breast cancer regression

Fasting-mimicking diet and hormone therapy induce breast cancer regression

  • Nature. 2020 Jul;583(7817):620-624. doi: 10.1038/s41586-020-2502-7.
Irene Caffa  # 1,  Vanessa Spagnolo  # 2 3,  Claudio Vernieri 3 4,  Francesca Valdemarin 1 5,  Pamela Becherini 1 5,  Min Wei 6,  Sebastian Brandhorst 6,  Chiara Zucal 7,  Else Driehuis 8 9,  Lorenzo Ferrando 5,  Francesco Piacente 1 5,  Alberto Tagliafico 10,  Michele Cilli 1,  Luca Mastracci 1 11,  Valerio G Vellone 1 11,  Silvano Piazza 7,  Anna Laura Cremonini 1 5,  Raffaella Gradaschi 1,  Carolina Mantero 1,  Mario Passalacqua 12,  Alberto Ballestrero 1 5,  Gabriele Zoppoli 1 5,  Michele Cea 1 5,  Annalisa Arrighi 5,  Patrizio Odetti 1 5,  Fiammetta Monacelli 1 5,  Giulia Salvadori 2 3,  Salvatore Cortellino 3,  Hans Clevers 8 9 13,  Filippo De Braud 2 4,  Samir G Sukkar 1,  Alessandro Provenzani 7,  Valter D Longo  # 14 15,  Alessio Nencioni  # 16 17
Affiliations

Affiliations

  • 1 IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • 2 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
  • 3 IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
  • 4 Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • 5 Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • 6 Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
  • 7 Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
  • 8 Oncode Institute and Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, The Netherlands.
  • 9 University Medical Center Utrecht, Utrecht, The Netherlands.
  • 10 Department of Health Sciences, University of Genoa, Genoa, Italy.
  • 11 Department of Integrated Surgical and Diagnostic Sciences, University of Genoa, Genoa, Italy.
  • 12 Department of Experimental Medicine, University of Genoa, Genoa, Italy.
  • 13 Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • 14 IFOM, FIRC Institute of Molecular Oncology, Milan, Italy. vlongo@usc.edu.
  • 15 Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA. vlongo@usc.edu.
  • 16 IRCCS Ospedale Policlinico San Martino, Genoa, Italy. alessio.nencioni@unige.it.
  • 17 Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. alessio.nencioni@unige.it.
  • # Contributed equally.
PMID: 32669709 DOI: 10.1038/s41586-020-2502-7
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-50767
    99.94%, CDK4/6抑制剂
    CDK
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