Mechanistically, we highlight how convergent signaling networks, including interleukin-6 (IL-6) family signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), interferon, and transforming growth factor-beta (TGF-β) pathways, couple to metabolic rewiring and chromatin reinforcement to stabilize pro-tumor phenotypes and define molecular inflection points during disease evolution. This evidence concerns the gene STAT3 and neoplasm.