For a long time, CAFs were only considered tumor promoters in the tumor microenvironment of the pancreatic cancer cells based on their involvement in tumor cell proliferation and survival via facilitating tumor invasion, metastasis, and immunosuppression.238,239 For example, as one of the traditional CAF activation pathways, the SHH pathway has been targeted by genetic deletion or chemical inhibition for tumor suppression. The gene discussed is SHH; the disease is neoplasm.