KIF20A in Human Malignancies: Oncogenic Mechanisms and Therapeutic Targeting Strategies

KIF20A is a key member of the kinesin family and is indispensable for the mitotic process. It governs cytokinesis, spindle dynamics, and centrosome integrity. KIF20A is frequently overexpressed in diverse human cancers, including pancreatic cancer, triple-negative breast cancer, and colorectal cancer, and so on. This overexpression correlates strongly with aggressive disease features such as advanced stage, metastasis, poor differentiation, and reduced patient survival. These features underscore its oncogenic role. Mechanistically, KIF20A promotes tumorigenesis through multiple pathways. It drives G2/M phase transition by interacting with Aurora B kinase and cyclin B1. KIF20A suppresses cell apoptosis by regulating Bcl-2 family protein expression. It induces Epithelial-Mesenchymal Transition (EMT) by controlling Snail and Twist signaling. KIF20A also enhances cell migration and invasion by modulating MMP-2 and MMP-9. It helps maintain cancer stem cell properties, such as self-renewal and chemoresistance. These factors fuel tumor recurrence. Given these functions, KIF20A is a promising therapeutic target. Current strategies include smallmolecule inhibitors, RNAi-based knockdown, and Antibody-Drug Conjugates (ADCs). Preclinical studies confirm that these approaches can suppress tumor growth in models. However, challenges remain, such as off-target effects on normal dividing cells and drug resistance. This review summarizes the molecular functions of KIF20A and its oncogenic mechanisms. It also discusses recent advances in targeting strategies. The review provides insights for developing effective anti-cancer therapies.