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Fasting-mimicking diet and hormone therapy induce breast cancer regression.
Caffa, Irene; Spagnolo, Vanessa; Vernieri, Claudio; Valdemarin, Francesca; Becherini, Pamela; Wei, Min; Brandhorst, Sebastian; Zucal, Chiara; Driehuis, Else; Ferrando, Lorenzo; Piacente, Francesco; Tagliafico, Alberto; Cilli, Michele; Mastracci, Luca; Vellone, Valerio G; Piazza, Silvano; Cremonini, Anna Laura; Gradaschi, Raffaella; Mantero, Carolina; Passalacqua, Mario; Ballestrero, Alberto; Zoppoli, Gabriele; Cea, Michele; Arrighi, Annalisa; Odetti, Patrizio; Monacelli, Fiammetta; Salvadori, Giulia; Cortellino, Salvatore; Clevers, Hans; De Braud, Filippo; Sukkar, Samir G; Provenzani, Alessandro; Longo, Valter D; Nencioni, Alessio.
Afiliação
  • Caffa I; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Spagnolo V; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
  • Vernieri C; IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
  • Valdemarin F; IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
  • Becherini P; Medical Oncology and Hematology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Wei M; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Brandhorst S; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Zucal C; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Driehuis E; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Ferrando L; Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
  • Piacente F; Longevity Institute, Leonard Davis School of Gerontology and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
  • Tagliafico A; Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
  • Cilli M; Oncode Institute and Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, The Netherlands.
  • Mastracci L; University Medical Center Utrecht, Utrecht, The Netherlands.
  • Vellone VG; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Piazza S; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Cremonini AL; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Gradaschi R; Department of Health Sciences, University of Genoa, Genoa, Italy.
  • Mantero C; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Passalacqua M; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Ballestrero A; Department of Integrated Surgical and Diagnostic Sciences, University of Genoa, Genoa, Italy.
  • Zoppoli G; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Cea M; Department of Integrated Surgical and Diagnostic Sciences, University of Genoa, Genoa, Italy.
  • Arrighi A; Department of Cellular, Computational, and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
  • Odetti P; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Monacelli F; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Salvadori G; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Cortellino S; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Clevers H; Department of Experimental Medicine, University of Genoa, Genoa, Italy.
  • De Braud F; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Sukkar SG; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Provenzani A; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Longo VD; Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
  • Nencioni A; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Nature ; 583(7817): 620-624, 2020 07.
Article em En | MEDLINE | ID: mdl-32669709
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Jejum / Dietoterapia / Fulvestranto Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nature Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Jejum / Dietoterapia / Fulvestranto Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Nature Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Itália