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Review | Open Access

Convergent systemic therapy for liver metastases: Bridging primary tumor heterogeneity through shared pathways

Wenjing Wanga,b,1Caiyun Penga,1Hongli Yua,bJiamin ChengaZhipeng LiangcYinying Lua ( )Zhixian Honga( )
Senior Department of Hepatology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100039, China
Senior Department of Hepatology, Chinese PLA General Hospital, Beijing 100039, China
The Clinical Medical School, Guizhou Medical University, Guiyang 561113, China

1 Wenjing Wang and Caiyun Peng contributed equally to this work.

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Abstract

Liver metastases represent a major clinical challenge in oncology, often indicating advanced disease with complex management requirements. Despite originating from diverse primary tumors such as colorectal, pancreatic, and breast cancers, liver metastases exhibit shared biological behaviors influenced by the unique tumor microenvironment and immunosuppressive conditions of the liver. This review synthesizes advances in systemic, locoregional, and surgical therapies, demonstrating how shared mechanisms enable unified strategies such as pathway-targeted agents and immunotherapy–radiotherapy combinations, even amid primary tumor heterogeneity. Multidisciplinary team collaboration is critical for optimizing individualized treatment plans, balancing locoregional and systemic treatments to convert unresectable cases and improve the survival rate. We propose a paradigm of precision convergence “harmonizing tumor therapies with lineage-specific adjustments” guided by the principle of “commonalities in biology, divergences in context”.

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iLIVER
Article number: 100204

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Cite this article:
Wang W, Peng C, Yu H, et al. Convergent systemic therapy for liver metastases: Bridging primary tumor heterogeneity through shared pathways. iLIVER, 2025, 4(4): 100204. https://doi.org/10.1016/j.iliver.2025.100204

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Received: 18 June 2025
Revised: 21 September 2025
Accepted: 20 October 2025
Published: 07 November 2025
© 2025 Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).