Ebastine for Adjuvant Treatment of Tumor Budding-Positive Liver Cancer After Surgery

Overview

This study evaluates ebastine, an FAK (focal adhesion kinase) inhibitor, as adjuvant therapy to reduce the risk of recurrence in patients with hepatocellular carcinoma (HCC) who have undergone curative hepatectomy and whose tumors show a histopathological feature known as tumor budding, which is associated with a higher risk of postoperative recurrence. Ebastine is a second-generation antihistamine approved for allergic conditions. Preclinical studies have shown that ebastine also inhibits FAK signaling, a pathway implicated in tumor invasion, epithelial-mesenchymal transition, and recurrence. This study investigates whether administering ebastine after surgery can lower the recurrence risk associated with tumor budding-positive HCC. All enrolled participants will receive ebastine as adjuvant treatment following hepatectomy. The primary endpoint is the 1-year recurrence-free survival (RFS) rate. Secondary endpoints include 2-year RFS, overall survival, and safety. All participants in this study will receive ebastine as adjuvant (after-surgery) treatment. Researchers will monitor whether the cancer stays away for at least one year after surgery (recurrence-free survival), as well as overall survival and any side effects.

Hepatocellular carcinoma (HCC) remains associated with a high rate of recurrence following curative hepatectomy, and tumor budding-a histopathological feature characterized by isolated single cells or small clusters of tumor cells at the invasive front-has been increasingly recognized as an independent adverse prognostic factor associated with epithelial-mesenchymal transition (EMT), local invasion, and early recurrence in multiple solid tumors, including HCC. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a central role in tumor cell adhesion, migration, invasion, and the EMT process that underlies tumor budding. FAK is frequently overexpressed and hyperactivated in HCC tissue and has been implicated in promoting a fibrotic, immunosuppressive tumor microenvironment that supports tumor progression and treatment resistance. Ebastine, a second-generation H1-antihistamine widely used for allergic rhinitis and urticaria with a well-characterized long-term safety profile, has recently been identified through drug-repurposing research as a small-molecule inhibitor of FAK. Preclinical studies have demonstrated that ebastine binds the tyrosine kinase domain of FAK, blocking autophosphorylation at Y397 and Y576/577 residues, thereby attenuating downstream FAK-mediated signaling (including JAK2/STAT3 and MEK/ERK pathways) that drives tumor stem-cell-like properties, invasion, and metastasis in several solid tumor models, including triple-negative and HER2-positive breast cancer. Given the mechanistic link between FAK signaling and tumor budding, and the favorable safety and tolerability profile of ebastine at its approved dose range, this study proposes to evaluate ebastine as an adjuvant therapy specifically in patients with tumor budding-positive HCC following curative hepatectomy-a population at elevated risk of early recurrence for whom effective, well-tolerated adjuvant options remain limited.