Department of Nutrition, University of California, Davis, CA 95616, USA.
Nutrients. 2021 Sep 15;13(9):3202. doi: 10.3390/nu13093202.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and extremely therapy-resistant cancer. It is estimated that up to 80% of PDAC patients present with cachexia, a multifactorial disorder characterized by the involuntary and ongoing wasting of skeletal muscle that affects therapeutic response and survival. During the last decade, there has been an increased interest in exploring dietary interventions to complement the treatment of PDAC and associated cachexia. Ketogenic diets (KDs) have gained attention for their anti-tumor potential. Characterized by a very low carbohydrate, moderate protein, and high fat composition, this diet mimics the metabolic changes that occur in fasting. Numerous studies report that a KD reduces tumor growth and can act as an adjuvant therapy in various cancers, including pancreatic cancer. However, research on the effect and mechanisms of action of KDs on PDAC-associated cachexia is limited. In this narrative review, we summarize the evidence of the impact of KDs in PDAC treatment and cachexia mitigation. Furthermore, we discuss key cellular mechanisms that explain KDs' potential anti-tumor and anti-cachexia effects, focusing primarily on reprogramming of cell metabolism, epigenome, and the gut microbiome. Finally, we provide a perspective on future research needed to advance KDs into clinical use.
胰腺导管腺癌（PDAC）是一种侵袭性和极具治疗抗性的癌症。据估计，多达 80%的 PDAC 患者出现恶病质，这是一种多因素紊乱，其特征为骨骼肌的非自愿性和持续消耗，影响治疗反应和生存。在过去十年中，人们越来越关注探索饮食干预措施来补充 PDAC 及其相关恶病质的治疗。生酮饮食（KDs）因其抗肿瘤潜力而受到关注。这种饮食的特点是极低的碳水化合物、中等蛋白质和高脂肪组成，模拟了禁食时发生的代谢变化。许多研究报告称，KD 可减少肿瘤生长，并可作为各种癌症（包括胰腺癌）的辅助治疗。然而，关于 KDs 对 PDAC 相关恶病质的作用和作用机制的研究有限。在这篇叙述性综述中，我们总结了 KDs 在 PDAC 治疗和恶病质缓解方面的影响证据。此外，我们讨论了解释 KDs 潜在抗肿瘤和抗恶病质作用的关键细胞机制，主要集中在细胞代谢、表观基因组和肠道微生物组的重编程上。最后，我们对推进 KDs 进入临床应用所需的未来研究提供了一个视角。
