Fasting-mimicking diet and hormone therapy induce breast cancer regression

被引:216
|
作者
Caffa, Irene [1 ]
Spagnolo, Vanessa [2 ,3 ]
Vernieri, Claudio [3 ,4 ]
Valdemarin, Francesca [1 ,5 ]
Becherini, Pamela [1 ,5 ]
Wei, Min [6 ,7 ]
Brandhorst, Sebastian [6 ,7 ]
Zucal, Chiara [8 ]
Driehuis, Else [9 ,10 ,11 ]
Ferrando, Lorenzo [5 ]
Piacente, Francesco [1 ,5 ]
Tagliafico, Alberto [12 ]
Cilli, Michele [1 ]
Mastracci, Luca [1 ,13 ]
Vellone, Valerio G. [1 ,13 ]
Piazza, Silvano [8 ]
Cremonini, Anna Laura [1 ,5 ]
Gradaschi, Raffaella [1 ]
Mantero, Carolina [1 ]
Passalacqua, Mario [14 ]
Ballestrero, Alberto
Zoppoli, Gabriele [1 ,5 ]
Cea, Michele [1 ,5 ]
Arrighi, Annalisa [5 ]
Odetti, Patrizio [1 ,5 ]
Monacelli, Fiammetta [1 ,5 ]
Salvadori, Giulia [2 ,3 ]
Cortellino, Salvatore [3 ]
Clevers, Hans [10 ,11 ,15 ]
De Braud, Filippo [2 ,4 ]
Sukkar, Samir G. [1 ]
Provenzani, Alessandro [8 ]
Longo, Valter D. [3 ,6 ,7 ]
Nencioni, Alessio [1 ,5 ]
机构
[1] IRCCS Osped Policlin San Martino, Genoa, Italy
[2] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy
[3] FIRC Inst Mol Oncol, IFOM, Milan, Italy
[4] Fdn IRCCS Ist Nazl Tumori, Med Oncol & Hematol Dept, Milan, Italy
[5] Univ Genoa, Dept Internal Med & Med Specialties, Genoa, Italy
[6] Univ Southern Calif, Leonard Davis Sch Gerontol, Longev Inst, Los Angeles, CA 90007 USA
[7] Univ Southern Calif, Dept Biol Sci, Los Angeles, CA 90007 USA
[8] Univ Trento, Dept Cellular Computat & Integrat Biol CIBIO, Trento, Italy
[9] Royal Netherlands Acad Arts & Sci, Oncode Inst, Utrecht, Netherlands
[10] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands
[11] Univ Med Ctr Utrecht, Utrecht, Netherlands
[12] Univ Genoa, Dept Hlth Sci, Genoa, Italy
[13] Univ Genoa, Dept Integrated Surg & Diagnost Sci, Genoa, Italy
[14] Univ Genoa, Dept Expt Med, Genoa, Italy
[15] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands
基金
美国国家卫生研究院;
关键词
ESTROGEN-RECEPTOR; GROWTH-FACTOR; RESISTANCE; INSULIN; LEPTIN; INHIBITORS; PALBOCICLIB; FULVESTRANT; METABOLISM; ACTIVATION;
D O I
10.1038/s41586-020-2502-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 benefit(1,2). Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet(3-5) 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.
引用
收藏
页码:620 / +
页数:22
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