Lu Mengxiao, Wu Yingjie, Xia MinMing, Zhang Yixin
Department of Gastrointestinal Minimally Invasive Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
Front Oncol. 2024 Nov 14;14:1454161. doi: 10.3389/fonc.2024.1454161. eCollection 2024.
Primary liver cancer (PLC), which includes hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Chronic liver diseases, such as hepatitis B and C infections and metabolic dysfunction-associated steatotic liver disease (MASLD), are key risk factors for PLC. Metabolic reprogramming, a defining feature of cancer, enables liver cancer cells to adapt to the demands of rapid proliferation and the challenging tumor microenvironment (TME). This manuscript examines the pivotal role of metabolic reprogramming in PLC, with an emphasis on the alterations in glucose, lipid, and amino acid metabolism that drive tumor progression. The Warburg effect, marked by increased glycolysis, facilitates rapid energy production and biosynthesis of cellular components in HCC. Changes in lipid metabolism, including elevated fatty acid synthesis and lipid oxidation, support membrane formation and energy storage essential for cancer cell survival. Amino acid metabolism, particularly glutamine utilization, supplies critical carbon and nitrogen for nucleotide synthesis and maintains redox homeostasis. These metabolic adaptations not only enhance tumor growth and invasion but also reshape the TME, promoting immune escape. Targeting these metabolic pathways presents promising therapeutic opportunities for PLC. This review underscores the interaction between metabolic reprogramming and tumor immunity, suggesting potential metabolic targets for innovative therapeutic strategies. A comprehensive understanding of PLC's intricate metabolic landscape may lead to more effective treatments and better patient outcomes. Integrating metabolomics, genomics, and proteomics in future research will be vital for identifying precise therapeutic targets and advancing personalized therapies for liver cancer.
原发性肝癌（PLC），包括肝细胞癌（HCC）和肝内胆管癌（iCCA），仍然是全球癌症相关死亡的主要原因。慢性肝病，如乙型和丙型肝炎感染以及代谢功能障碍相关脂肪性肝病（MASLD），是PLC的关键危险因素。代谢重编程作为癌症的一个决定性特征，使肝癌细胞能够适应快速增殖的需求和具有挑战性的肿瘤微环境（TME）。本文探讨了代谢重编程在PLC中的关键作用，重点关注驱动肿瘤进展的葡萄糖、脂质和氨基酸代谢的改变。以糖酵解增加为特征的瓦伯格效应促进了HCC中细胞成分的快速能量产生和生物合成。脂质代谢的变化，包括脂肪酸合成增加和脂质氧化，支持癌细胞存活所必需的膜形成和能量储存。氨基酸代谢，特别是谷氨酰胺的利用，为核苷酸合成提供关键的碳和氮，并维持氧化还原稳态。这些代谢适应不仅增强了肿瘤的生长和侵袭，还重塑了TME，促进免疫逃逸。针对这些代谢途径为PLC提供了有前景的治疗机会。本综述强调了代谢重编程与肿瘤免疫之间的相互作用，为创新治疗策略提出了潜在的代谢靶点。对PLC复杂代谢格局的全面理解可能会带来更有效的治疗方法和更好的患者预后。在未来的研究中整合代谢组学、基因组学和蛋白质组学对于确定精确的治疗靶点和推进肝癌的个性化治疗至关重要。
