SHH and central nervous system cancer: Brain tumor and other neoplasm in nervous system account for 1.6% new cases worldwide in 2020 and lead to more than 251,329 deaths.185 Two types of malignant primary brain tumors including medulloblastoma (MB) and glioma were in close relationship with HH signaling pathway.221 MB is a common aggressive malignant tumor in brain during childhood.222 There are four subtypes of MB based on research on their molecular mechanism and clinical characteristics: Wnt-MB, Shh-MB, group 3 MB and group 4 MB.223 The novel feature of Shh-MB is constitutive activation of the Shh signaling pathway.