Department of Family, Population & Preventive Medicine, Stony Brook University, Stony Brook, NY, United States.
Department of Pathology, Stony Brook University, Stony Brook, NY, United States; Stony Brook Cancer Center, Stony Brook, NY, United States.
Int Rev Cell Mol Biol. 2022;373:1-36. doi: 10.1016/bs.ircmb.2022.02.004. Epub 2022 Mar 31.
Limiting nutrient utilization by cancer cells in order to disrupt their metabolism and suppress their growth represents a promising approach for anti-cancer therapy. Recently, studies demonstrating the anti-neoplastic effects of lowering amino acid (AA) availability have opened up an exciting and quickly growing field of study. Although intracellular synthesis can often provide the AAs necessary to support cancer cells, diet and the tumor microenvironment can also be important sources. In fact, studies carried out in vitro and in animal tumor models have supported the anti-cancer potential of restricting exogenous sources of AAs. However the potential benefit of reducing AA intake in cancer patients requires further investigation. Furthermore, implementation of such an approach clinically, even if proven useful, could be challenging. In the enclosed review, we (1) summarize the pre-clinical studies showing the anti-tumorigenic effects of restricting exogenously available AAs, including through reducing dietary protein, (2) consider the role of microbiota in this process, (3) report on current recommendations for protein intake in cancer patients and studies that applied these guidelines, and (4) propose considerations for studies to test the potential therapeutic benefit of reducing protein/AA consumption in patients with cancer.
限制癌细胞对营养物质的利用,以破坏其代谢并抑制其生长,这代表了一种有前途的抗癌治疗方法。最近,研究表明降低氨基酸(AA)可用性具有抗肿瘤作用,这开辟了一个令人兴奋且快速发展的研究领域。尽管细胞内合成通常可以提供支持癌细胞所需的氨基酸,但饮食和肿瘤微环境也可能是重要的来源。事实上,在体外和动物肿瘤模型中进行的研究支持了限制外源性氨基酸来源的抗癌潜力。然而,减少癌症患者 AA 摄入的潜在益处需要进一步研究。此外,即使这种方法被证明有用,在临床上实施也可能具有挑战性。在本综述中,我们(1)总结了表明限制外源性可用氨基酸(包括通过减少饮食蛋白)具有抗肿瘤作用的临床前研究,(2)考虑了微生物组在这一过程中的作用,(3)报告了目前癌症患者蛋白质摄入量的建议和应用这些指南的研究,以及(4)提出了一些考虑因素,用于研究减少癌症患者蛋白质/氨基酸消耗的潜在治疗益处。