Anlotinib in cancer therapy: mechanisms of action, clinical applications, and future perspectives

This comprehensive review examines anlotinib, a novel multi-target receptor tyrosine kinase inhibitor with potent antitumor activity. Anlotinib selectively inhibits multiple targets including VEGFR1-3, PDGFR-α, c-Kit, and FGFR1-3, demonstrating superior inhibitory effects compared to other tyrosine kinase inhibitors. The review explores anlotinib’s multifaceted mechanisms of action: inhibition of angiogenesis through disruption of VEGF/PDGF/FGF pathways, suppression of tumor cell migration and invasion via modulation of various signaling cascades, induction of apoptosis through multiple pathways, inhibition of lymphangiogenesis primarily through VEGFR-3 modulation, and positive modulation of the tumor microenvironment. The article further discusses anlotinib’s promising ability to overcome chemoresistance through regulation of drug efflux systems, pro-survival signaling, cancer stemness, and autophagy. The review highlights the synergistic effects of anlotinib in combination therapies with radiochemotherapy, immune checkpoint inhibitors, and targeted drugs across multiple cancer types. Despite its promising efficacy, challenges including low response rates and potential for acquired resistance remain. Future research directions should focus on optimizing dosing regimens, identifying predictive biomarkers, exploring novel combinations, investigating resistance mechanisms, and evaluating anlotinib’s potential in neoadjuvant or adjuvant settings. This extensive analysis provides insights into anlotinib’s therapeutic potential in solid tumors and hematological malignancies, paving the way for more effective and personalized cancer treatment strategies.