禁食和模仿禁食的饮食可以延长老鼠模型的寿命和健康寿命，降低人类患癌症和其他与年龄有关的病理因素的风险。正常细胞对禁食和随之而来的营养减少做出反应，通过下调原癌基因途径进入抗压状态，这种状态可以保护它们免受不同癌症治疗的伤害。相反，癌基因突变和包括RAS、AKT和PKA在内的途径的固有激活使得癌细胞不遵守禁食相关的抗生长信号。重要的是，在不同的肿瘤类型中，禁食通过增加反应性氧化物和氧化应激的产生，从而导致DNA损伤和细胞死亡，增强了各种治疗的毒性作用。这种效应不仅局限于化疗，由于周期性禁食和模仿禁食饮食可以增强酪氨酸激酶抑制剂、激素疗法、放射疗法和药物剂量的维生素C的作用。此外，禁食/模仿禁食的抗癌效应也可能是肿瘤无关的，涉及到T细胞依赖性攻击肿瘤细胞的免疫疗法的激活。在一系列临床前研究的支持下，临床试验开始确认禁食/模仿禁食周期的安全性和有效性，在提高不同癌症治疗的潜力的同时，降低对健康细胞和组织的副作用。Copyright © 2022 Elsevier Inc. All rights reserved.

Fasting and fasting mimicking diets extend lifespan and healthspan in mouse models and decrease risk factors for cancer and other age-related pathologies in humans. Normal cells respond to fasting and the consequent decrease in nutrients by down-regulating proto-oncogene pathways to enter a stress-resistant mode, which protects them from different cancer therapies. In contrast, oncogene mutations and the constitutive activation of pathways including RAS, AKT, and PKA allow cancer cells to disobey fasting-dependent anti-growth signal. Importantly, in different tumor types, fasting potentiates the toxicity of various therapies by increasing reactive oxygen species and oxidative stress, which ultimately leads to DNA damage and cell death. This effect is not limited to chemotherapy, since periodic fasting/FMD cycles potentiate the effects of tyrosine kinase inhibitors, hormone therapy, radiotherapy, and pharmacological doses of vitamin C. In addition, the anticancer effects of fasting/FMD can also be tumor-independent and involve an immunotherapy-like activation of T cell-dependent attack of tumor cells. Supported by a range of pre-clinical studies, clinical trials are beginning to confirm the safety and efficacy of fasting/FMD cycles in improving the potential of different cancer therapies, while decreasing side effects to healthy cells and tissues.Copyright © 2022 Elsevier Inc. All rights reserved.