Paired mesoderm homeobox protein 2B (PHOX2B) (PHOX2B)

Paired mesoderm homeobox protein 2B (PHOX2B) is a master transcription factor essential for the development of the autonomic nervous system, particularly noradrenergic neurons. It is highly expressed during embryogenesis but becomes largely silenced in most adult tissues, making it a highly specific marker for neuroblastoma and other neurocristopathies [1, 8]. In neuroblastoma, PHOX2B acts as an oncogenic driver by maintaining cells in an undifferentiated, proliferative state, and its expression levels are used clinically to monitor minimal residual disease [3, 12]. While its intracellular nature historically made it difficult to target, novel peptide-centric chimeric antigen receptor (PC-CAR) T-cell therapies have been developed to recognize PHOX2B-derived peptides presented on the cell surface by HLA molecules [9, 18]. Additionally, small molecules such as chloroquine and retinoic acid have been shown to downregulate PHOX2B expression, thereby promoting tumor cell differentiation and apoptosis [12, 14].

Other names

PMX2BNBPhoxNBLST2Paired-like homeobox 2BNeuroblastoma Phox

Immunotherapeutic targeting of intracellular protein fragments via peptide-centric chimeric antigen receptor (PC-CAR) T-cells and pharmacological downregulation of gene expression to induce tumor cell differentiation.