CXCR4, is overexpressed in many cancers and plays a key role in tumor dissemination, stem cell maintenance, and therapy resistance. Ulocuplumab’s blockade of CXCR4 signaling aims to mobilize cancer cells from protective niches (e.g., bone marrow), sensitize them to chemotherapy, and reduce metastatic spread. While clinical development has faced challenges, it represents a targeted approach to disrupt microenvironmental protection in aggressive cancers.