HOXC6 is a sequence-specific transcription factor that functions as a developmental master gene controlling anterior-posterior axis patterning and cell differentiation 1. The HOXC6 gene produces two protein isoforms sharing a conserved DNA-binding homeodomain but differing in their N-terminal regions, enabling both transcriptional activation and repression depending on cellular context and interactions with other HOX family members and co-factors 1. During normal development, HOXC6 expression is upregulated during neuroblast differentiation induced by retinoic acid and cyclic AMP 2. In cancer pathology, HOXC6 functions as an oncogene across multiple malignancies. In colorectal cancer, HOXC6 overexpression promotes metastasis in microsatellite instability-high tumors by upregulating CCL2 to recruit M2 macrophages, which subsequently induce epithelial-mesenchymal transition and T-cell exhaustion 3. In head and neck squamous cell carcinoma, HOXC6 increases Bcl-2 expression via TAAT motifs in the Bcl-2 promoter, enhancing anti-apoptotic signaling and chemotherapy resistance 4. HOXC6 overexpression correlates with poor prognosis and reduced migration in HNSCC through dysregulation of E2F and G2M cell cycle checkpoints 5. In hepatocellular carcinoma and multiple myeloma, HOXC6 knockdown suppresses proliferation, migration, and inflammatory pathways via NF-κB inactivation 6 7. In BRAFV600E colorectal cancer, HOXC6 regulates MYC expression and contributes to treatment resistance 8. These findings establish HOXC6 as a promising therapeutic target across solid and hematologic malignancies.