This phenotypic shift is driven by upregulated SOX2, a reprogramming transcription factor, and can be reversed by restoring TP53 and RB1 function or inhibiting SOX2 expression.51,52,54 Together, TP53 and RB1 maintain differentiation and suppress plasticity; their disruption creates a microenvironment conducive to tumor evolution, with implications for disease aggressiveness and resistance to therapy.55 Here, SOX2 is linked to neoplasm.