In the current study, we documented the role of IL-6/IL-6R/gp130/STAT3 signaling in CAC, investigated whether SHH inhibitors can abrogate oncogenic IL-6 signaling, impose anti-inflammatory effects, preserve 15-hydroxyprostaglandin dehydrogenase (15-PGDH as confidential tumor-suppressive pathways, induce apoptosis through Gli-1–dependent down-regulation of Bcl-2, and kill CSC presented in colosphere xenografts. The gene discussed is HPGD; the disease is neoplasm.