极少数代谢产物可以像乙酰辅酶A（乙酰-CoA）一样在细胞代谢中拥有如此重要和多功能的作用。乙酰-CoA在营养物质分解过程中产生，以供给三羧酸循环的能量，并且是合成脂肪酸和异戊二烯生物合成的必要组成部分。它还作为信号代谢产物，作为赖氨酸乙酰化反应的底物，可以在响应乙酰-CoA的可用性下调节蛋白质的功能。近年来，我们对正常生理和癌症中乙酰-CoA代谢的理解取得了令人兴奋的进展，这得益于新的小鼠模型、体内稳定同位素示踪方法和改进的乙酰-CoA测量方法，包括在特定亚细胞区域中的测量。针对乙酰-CoA代谢酶的靶向努力也在不断推进，其中一种针对乙酰-CoA合成的治疗剂已获得美国食品和药品管理局的批准。在本综述中，我们概述了乙酰-CoA参与的主要代谢途径的调节和癌症相关性。我们进一步讨论了最近对正常组织和肿瘤中乙酰-CoA代谢的理解取得的进展，以及针对这些途径进行治疗的潜力。最后，我们评论了乙酰-CoA代谢中出现的新的节点，可能会影响癌症生物学。©2023年Springer Nature Limited.

Few metabolites can claim a more central and versatile role in cell metabolism than acetyl coenzyme A (acetyl-CoA). Acetyl-CoA is produced during nutrient catabolism to fuel the tricarboxylic acid cycle and is the essential building block for fatty acid and isoprenoid biosynthesis. It also functions as a signalling metabolite as the substrate for lysine acetylation reactions, enabling the modulation of protein functions in response to acetyl-CoA availability. Recent years have seen exciting advances in our understanding of acetyl-CoA metabolism in normal physiology and in cancer, buoyed by new mouse models, in vivo stable-isotope tracing approaches and improved methods for measuring acetyl-CoA, including in specific subcellular compartments. Efforts to target acetyl-CoA metabolic enzymes are also advancing, with one therapeutic agent targeting acetyl-CoA synthesis receiving approval from the US Food and Drug Administration. In this Review, we give an overview of the regulation and cancer relevance of major metabolic pathways in which acetyl-CoA participates. We further discuss recent advances in understanding acetyl-CoA metabolism in normal tissues and tumours and the potential for targeting these pathways therapeutically. We conclude with a commentary on emerging nodes of acetyl-CoA metabolism that may impact cancer biology.© 2023. Springer Nature Limited.