Lenvatinib Exhibits Potent Anti-tumor Activity and Favorable Safety Profile in a Colorectal Cancer Xenograft Model

BACKGROUND/AIM: Lenvatinib, a multikinase inhibitor, has shown potential anti-tumor activity in various cancers. This study evaluated its efficacy, safety, and apoptotic mechanisms in colorectal cancer (CRC) using HT-29 xenograft-bearing mice. MATERIALS AND METHODS: Mice were treated with lenvatinib at 0, 10, or 20 mg/kg for 20 days. Tumor growth, serum biochemistry, and histopathology were assessed. Protein expression related to ERK signaling and apoptosis was analyzed using immunohistochemistry. RESULTS: Lenvatinib significantly suppressed CRC tumor growth, delaying progression up to 14-fold compared with controls. No body-weight loss or hepatic/renal toxicity was observed, indicating good tolerability. Mechanistically, lenvatinib reduced phosphorylated ERK and anti-apoptotic proteins (BCL-2, c-FLIP, XIAP) by 30-50%, while enhancing cleaved caspase-3, -8, -9, BAX, and BAK expression by 1.2-1.5-fold, promoting apoptosis. CONCLUSION: Lenvatinib exhibits potent anti-CRC activity with minimal systemic toxicity. Its therapeutic effects are mediated through ERK pathway inactivation, suppression of anti-apoptotic proteins, and induction of caspase-dependent apoptosis.