意大利热那亚大学Alessio Nencioni、Valter D. Longo等研究人员合作发现，禁食模拟饮食和激素疗法可导致乳腺癌消退。该项研究成果于2020年7月15日在线发表在《自然》杂志上。
研究人员发现，在荷尔蒙受体阳性乳腺癌的小鼠模型中，定期空腹或禁食模拟饮食可通过降低循环的IGF1、胰岛素和瘦素并过上调EGR1和PTEN来抑制 AKT–mTOR信号，从而增强内分泌疗法他莫昔芬和氟维司群的活性。当氟维司群与palbociclib（一种细胞周期蛋白依赖性激酶4/6抑制剂）联合使用时，增加定期禁食模拟饮食的周期可促进持久的肿瘤消退并恢复对药物治疗的获得性耐药。
此外，禁食和禁食模拟的饮食方案都可以预防他莫昔芬引起的子宫内膜增生。在接受雌激素治疗的荷尔蒙受体阳性乳腺癌患者中，禁食模拟饮食的周期会导致代谢变化，类似于在小鼠中观察到的变化，包括胰岛素、瘦素和IGF1的水平降低，并使得后二者长期处于低水平。在小鼠中，这些持久作用与长期抗癌活性有关。
这些结果表明，禁食模拟饮食可作为激素受体阳性乳腺癌中雌激素治疗佐剂进行进一步临床研究。
据了解，所有乳腺癌中约有75％表达雌激素和/或孕激素受体。内分泌疗法通常对这些激素受体阳性肿瘤有效，但原发性和获得性耐药限制了其疗效。
附：英文原文
Title: Fasting-mimicking diet and hormone therapy induce breast cancer regression
Author: 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 De Braud, Samir G. Sukkar, Alessandro Provenzani, Valter D. Longo, Alessio Nencioni
Issue&Volume: 2020-07-15
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 diet3,4,5 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.
DOI: 10.1038/s41586-020-2502-7
Source: https://www.nature.com/articles/s41586-020-2502-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
