Université Caen Normandie, Medical School, CHU de Caen, Caen, France.
Normandie Université, UNICAEN, INSERM U1086, Interdisciplinary Research Unit for Cancer Prevention and Treatment, Centre de Lutte Contre le Cancer Centre François Baclesse, Caen, France.
Adv Nutr. 2021 Jul 30;12(4):1461-1480. doi: 10.1093/advances/nmaa174.
The tumor microenvironment is a complex mix of cancerous and noncancerous cells (especially immune cells and fibroblasts) with distinct metabolisms. These cells interact with each other and are influenced by the metabolic disorders of the host. In this review, we discuss how metabolic pathways that sustain biosynthesis in cancer cells could be targeted to increase the effectiveness of cancer therapies by limiting the nutrient uptake of the cell, inactivating metabolic enzymes (key regulatory ones or those linked to cell cycle progression), and inhibiting ATP production to induce cell death. Furthermore, we describe how the microenvironment could be targeted to activate the immune response by redirecting nutrients toward cytotoxic immune cells or inhibiting the release of waste products by cancer cells that stimulate immunosuppressive cells. We also examine metabolic disorders in the host that could be targeted to inhibit cancer development. To create future personalized therapies for targeting each cancer tumor, novel techniques must be developed, such as new tracers for positron emission tomography/computed tomography scan and immunohistochemical markers to characterize the metabolic phenotype of cancer cells and their microenvironment. Pending personalized strategies that specifically target all metabolic components of cancer development in a patient, simple metabolic interventions could be tested in clinical trials in combination with standard cancer therapies, such as short cycles of fasting or the administration of sodium citrate or weakly toxic compounds (such as curcumin, metformin, lipoic acid) that target autophagy and biosynthetic or signaling pathways.
肿瘤微环境是由癌细胞和非癌细胞（尤其是免疫细胞和成纤维细胞）组成的复杂混合物，它们具有不同的代谢方式。这些细胞相互作用，并受到宿主代谢紊乱的影响。在这篇综述中，我们讨论了如何通过限制细胞的营养摄取、使代谢酶失活（关键调节酶或与细胞周期进展相关的酶）以及抑制 ATP 产生来诱导细胞死亡，从而靶向维持癌细胞生物合成的代谢途径，以提高癌症治疗的效果。此外，我们还描述了如何通过将营养物质重新导向细胞毒性免疫细胞或抑制癌细胞释放刺激免疫抑制细胞的废物，靶向微环境以激活免疫反应。我们还研究了宿主中的代谢紊乱，这些紊乱可以被靶向以抑制癌症的发展。为了为每个肿瘤创造未来的个性化治疗方法，必须开发新的技术，例如正电子发射断层扫描/计算机断层扫描的新型示踪剂和免疫组织化学标志物，以表征癌细胞及其微环境的代谢表型。在等待针对患者癌症发展的所有代谢成分的个性化策略的同时，可以在临床试验中结合标准癌症疗法测试简单的代谢干预措施，例如短暂的禁食周期或给予柠檬酸钠或弱毒性化合物（如姜黄素、二甲双胍、硫辛酸），这些化合物可以靶向自噬和生物合成或信号通路。
