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模仿禁食的饮食和激素治疗诱导乳腺癌的回归

Irene Caffa¹, Vanessa Spagnolo^2,3, Claudio Vernieri^3,4

¹IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

|July 17, 2020

概括

定期禁食或模仿禁食的饮食可以增强激素受体阳性乳腺癌的内分泌疗法. 这种方法可以帮助克服耐药性和预防副作用,为患者提供新的希望.

科学领域:

癌症学
代谢研究
内分泌学

背景情况:

大多数乳腺癌 (约. 75%) 是荷尔蒙受体阳性的.
内分泌疗法是有效的,但由于原发性和获得性耐药性而受到限制.
需要新的策略来改善这些患者的长期结果.

研究的目的:

研究定期禁食或仿禁食饮食 (FMD) 作为激素受体阳性乳腺癌内分泌治疗的辅助剂的有效性.
阐明禁食诱导的内分泌疗法的潜在分子机制.
评估口病对耐药性和与治疗相关的副作用的影响.

主要方法:

使用激素受体阳性乳腺癌的小鼠模型.
与坦莫西芬和富尔韦斯坦一起定期禁食或口.
研究了循环激素 (IGF1,胰岛素,瘦素) 和信号通路 (AKT-mTOR,EGR1,PTEN) 的变化.
评估了小鼠的瘤回归,获得的耐药性和子宫内膜增生.
在接受雌激素治疗和口周期的激素受体阳性乳腺癌患者中评估代谢变化.

主要成果:

定期禁食/ FMD 通过降低 IGF1,胰岛素和素,并抑制 AKT- mTOR 信号,增强了塔莫西芬和富勒弗兰特的疗效.
禁食/ FMD 逆转了与palbociclib 结合的富尔韦斯特兰特所获得的耐药性,促进了长期的瘤回归.
在小鼠中禁食/ FMD 预防了泰莫西芬诱导的子宫内膜增生.
人类患者表现出类似的代谢变化 (降低胰岛素,瘦素,IGF1).
长期的代谢变化与持续的抗癌活性相关.

结论:

定期禁食和口病显示出作为激素受体阳性乳腺癌的辅助疗法的巨大潜力.
基于禁食的干预措施可以克服内分泌疗法耐药性并减轻副作用.
需要进一步的临床研究来探索口病作为雌激素治疗的辅助.

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