Supplementary Material for: Traditional Chinese Medicine in the Management of Colorectal Cancer Liver Metastasis: Mechanisms, Challenges, and Perspectives

Background: Colorectal cancer (CRC) is a leading global malignancy, with the liver being the primary site of distant metastasis. Colorectal cancer liver metastasis (CRLM) is the predominant cause of mortality in CRC patients. Emerging evidence underscores the complexity of CRLM mechanisms, where the tumor microenvironment (TME) plays a central role in driving metastasis and fostering treatment resistance. Current Western medical strategies (chemotherapy, targeted therapy, immunotherapy, surgery) offer limited disease control, often accompanied by adverse effects, and lack specific pharmacological interventions targeting CRLM effectively. Summary: This review systematically evaluates the potential of Traditional Chinese Medicine (TCM) – guided by holistic and syndrome differentiation principles – as a therapeutic approach for CRLM. By analyzing literature from PubMed, Web of Science, Embase, CNKI, and Wanfang databases, we find that TCM interventions (formulas, herb pairs, phytochemicals) exert therapeutic effects by modulating the TME through multiple mechanisms. These include inhibiting extracellular matrix (ECM) remodeling, suppressing hypoxia-induced angiogenesis, and reversing immune evasion. Key Message: TCM exhibits unique multi-component, multi-target, and multi-pathway advantages against CRLM, presenting a promising complementary strategy. Future high-quality research, particularly well-designed clinical trials, is essential to validate efficacy, understand mechanisms further, and translate the potential of TCM into clinically meaningful benefits for CRLM patients.