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Lenvatinib + losartan is a combination therapy being investigated as a postoperative adjuvant treatment for hepatocellular carcinoma (HCC), specifically in patients with positive tumor budding. Lenvatinib is a potent multi-kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR1-3), fibroblast growth factor receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET, thereby inhibiting tumor angiogenesis and proliferation. Losartan, traditionally an angiotensin II receptor blocker (ARB) used for hypertension, is utilized in this context for its ability to degrade collagen barriers within the peritumoral stroma. This "collagen degradation therapy" is intended to reduce the physical resistance of the tumor microenvironment, facilitating better delivery and penetration of lenvatinib into tumor-bottle lesions. The combination is currently being evaluated in a Phase 4 clinical trial led by the Second Affiliated Hospital of Xi'an Jiaotong University to improve survival outcomes and reduce recurrence rates in high-risk HCC patients.
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