Xu Wenchao, Xu Jia, Liu Jianzhou, Wang Nanzhou, Zhou Li, Guo Junchao
Department of General Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
Key Laboratory of Research in Pancreatic Tumor Chinese Academy of Medical Sciences Beijing China.
MedComm (2020). 2025 Feb 27;6(3):e70119. doi: 10.1002/mco2.70119. eCollection 2025 Mar.
Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic-friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.
肝转移是恶性肿瘤致死的主要原因,严重影响治疗干预的效果。近年来,临床前和临床研究在理解肝转移的分子机制和治疗策略方面均取得了重大进展。来自不同原发部位的转移性肿瘤细胞经历高度相似的生物学过程,最终在肝脏中实现异位定植和生长。在这篇综述中,我们首先介绍肝脏固有的利于转移的特征。然后,我们探讨肝转移的全貌,并基于肝脏对转移的反应总结出三个连续但不同的阶段。这包括转移感知阶段、转移应激阶段和转移支持阶段。我们讨论转移性肿瘤细胞与各种驻留细胞和募集细胞之间复杂的相互作用。此外,我们强调免疫细胞空间重塑在肝转移中的关键作用。最后,我们回顾了肝转移临床管理方面的最新进展和面临的挑战。未来精确的抗转移治疗应充分考虑个体异质性,并根据肝转移的阶段实施不同的靶向干预措施。