The B-cell lymphoma 9 (BCL9) protein is a transcriptional coactivator that plays a critical role in the Wnt/β-catenin signaling pathway, a key pathway regulating cell proliferation, differentiation, and stemness. Dysregulation of this pathway is implicated in various cancers, including colorectal, hepatocellular, and hematologic malignancies. BCL9 interacts with β-catenin to enhance its nuclear translocation and transcriptional activity, driving the expression of oncogenes like c-Myc and cyclin D1. Elevated BCL9 expression is associated with tumor progression, metastasis, and poor prognosis.
BCL9 antibodies are tools developed to target this oncogenic mechanism. They aim to disrupt the BCL9-β-catenin interaction, thereby suppressing aberrant Wnt signaling. Preclinical studies show that inhibiting BCL9 with antibodies or small molecules reduces tumor growth and metastasis in animal models, particularly in cancers with hyperactive Wnt pathways. These antibodies also serve as research reagents to study BCL9's role in development and disease. However, challenges remain, including optimizing specificity, delivery efficiency, and addressing potential compensatory pathways. While still largely experimental, BCL9 antibodies represent a promising therapeutic strategy for Wnt-driven cancers, offering an alternative to conventional pathway inhibitors.