HOXB3 is a sequence-specific transcription factor that functions as a developmental regulator providing cells with anterior-posterior positional identity 1. It contains a homeodomain that binds DNA at conserved TAATTA consensus sequences and positively regulates target genes including Otx2 1. Beyond developmental roles in embryonic skeletal system morphogenesis and angiogenesis, HOXB3 has emerged as a critical oncogenic factor in multiple cancers. In castration-resistant prostate cancer, elevated HOXB3 independently predicts PSA progression and death by driving WNT pathway activation and abiraterone resistance 2. In ovarian cancer, HOXB3 overexpression is associated with chemotherapy resistance through a STUB1/HOXB3/PARK7 axis, where HOXB3 transcriptionally activates PARK7 to suppress ferroptosis 3. HOXB3 expression elevation correlates with reduced platinum sensitivity and diminished chemotherapy-induced reactive oxygen species in high-grade serous ovarian cancer, with HOXA4/HOXB3 co-expression predicting poor progression-free survival 4. In glioblastoma, HOXB3 forms transcriptional condensates that drive oncogenic super-enhancer activity, and disrupting HOXB3 condensation with peptide inhibitors reduces tumorigenicity in patient-derived xenografts 5. These findings suggest HOXB3 as a therapeutic target across multiple malignancies.