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.

背景：结直肠癌（Colorectal cancer, CRC）是全球高发的恶性肿瘤之一，肝脏为其远处转移的主要靶部位。结直肠癌肝转移（Colorectal cancer liver metastasis, CRLM）是结直肠癌患者死亡的主要诱因。越来越多的研究证据表明，结直肠癌肝转移的发病机制极为复杂，肿瘤微环境（Tumor Microenvironment, TME）在推动转移进程及介导治疗抵抗方面发挥着核心作用。当前西医治疗策略（化疗、靶向治疗、免疫治疗、手术治疗）的疾病控制效果有限，且常伴随多种不良反应，目前尚缺乏可有效靶向结直肠癌肝转移的特异性药物干预手段。
综述概要：本综述系统评估了以整体观念与辨证论治为核心原则的中医药（Traditional Chinese Medicine, TCM）用于结直肠癌肝转移治疗的潜在价值。通过检索PubMed、Web of Science、Embase、中国知网（CNKI）及万方数据等数据库的相关文献，本研究发现中医药干预方案（包括方剂、药对、植物化学成分）可通过多重机制调控肿瘤微环境，进而发挥治疗效应，具体涵盖抑制细胞外基质（Extracellular Matrix, ECM）重塑、抑制缺氧诱导的血管生成以及逆转免疫逃逸。
核心观点：中医药具有多组分、多靶点、多通路的独特治疗优势，可为结直肠癌肝转移提供极具前景的补充治疗策略。未来需开展高质量研究，尤其是设计严谨的临床试验，以验证其临床疗效、进一步阐明作用机制，并将中医药的治疗潜力转化为结直肠癌肝转移患者切实可及的临床获益。