Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
Cell Cycle. 2010 Nov 15;9(22):4474-6. doi: 10.4161/cc.9.22.13954.
Chronic calorie restriction has been known for decades to prevent or retard cancer growth, but its weight-loss effect and the potential problems associated with combining it with chemotherapy have prevented its clinical application. Based on the discovery in model organisms that short term starvation (STS or fasting) causes a rapid switch of cells to a protected mode, we described a fasting-based intervention that causes remarkable changes in the levels of glucose, IGF-I and many other proteins and molecules and is capable of protecting mammalian cells and mice from various toxins, including chemotherapy. Because oncogenes prevent the cellular switch to this stress resistance mode, starvation for 48 hours or longer protects normal yeast and mammalian cells and mice but not cancer cells from chemotherapy, an effect we termed Differential Stress Resistance (DSR). In a recent article, 10 patients who fasted in combination with chemotherapy, reported that fasting was not only feasible and safe but caused a reduction in a wide range of side effects accompanied by an apparently normal and possibly augmented chemotherapy efficacy. Together with the remarkable results observed in animals, these data provide preliminary evidence in support of the human application of this fundamental biogerontology finding, particularly for terminal patients receiving chemotherapy. Here we briefly discuss the basic, pre-clinical, and clinical studies on fasting and cancer therapy.
几十年来，人们已经知道慢性卡路里限制可以预防或延缓癌症的生长，但由于其减肥效果以及与化疗结合可能带来的问题，限制了其在临床上的应用。基于在模式生物中发现的短期饥饿（STS 或禁食）会导致细胞迅速切换到保护模式的发现，我们描述了一种基于禁食的干预措施，该措施会导致葡萄糖、IGF-I 和许多其他蛋白质和分子的水平发生显著变化，并能够保护哺乳动物细胞和小鼠免受各种毒素的侵害，包括化疗。由于致癌基因阻止细胞切换到这种应激抗性模式，因此禁食 48 小时或更长时间可以保护正常酵母和哺乳动物细胞和小鼠免受化疗的侵害，但不能保护癌细胞免受化疗的侵害，我们将这种效应称为差异应激抗性（DSR）。在最近的一篇文章中，10 名接受化疗和禁食联合治疗的患者报告说，禁食不仅可行且安全，而且还降低了广泛的副作用，同时化疗效果似乎正常且可能增强。这些数据与动物身上观察到的显著结果一起，为这一基本的生物衰老学发现的人体应用提供了初步证据，特别是对接受化疗的晚期患者。在这里，我们简要讨论了关于禁食和癌症治疗的基础、临床前和临床研究。
