Liver Metastasis in Cancer: Molecular Mechanisms and Management

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.