• What is SMO?
  • SMO in Medulloblastoma
  • Clinical Trials


SMO is a component of the Hedgehog signaling pathway (Figure 1). SMO and PTCH1 are transmembrane receptor proteins that deliver signals from Hedgehog ligands to cells. Mutations in PTCH1 or SMO that lead to constitutive activation of SMO are known to play a role in carcinogenesis of basal cell carcinoma, glioblastoma, medulloblastoma, and rhabdomyosarcoma (Onishi and Katano 2011).

The Hedgehog signaling pathway is a critical part of embryonic development (Athar et al. 2006). In skin, Hedgehog proteins are involved in maintenance of stem cells, development of hair follicles, development of glands, and regulation of skin growth (Athar et al. 2006).

After embryonic development, the Hedgehog pathway is not active in most human tissues (Rudin 2012). Reactivation of this pathway can lead or contribute to carcinogenesis (Onishi and Katano 2011).

SMO was identified as a therapeutic target by Hahn et al. (1996) and Johnson et al. (1996) (Rudin 2012). SMO inhibitors, exemplified by cyclopamine, bind strongly to the SMO receptor, which results in suppression of Hedgehog signaling (Robarge et al. 2009; Rudin 2012).


Figure 1. Schematic of the Hedgehog signaling pathway.

Related Pathways

Contributors: Charles Rudin, M.D., Ph.D.

Suggested Citation: Rudin, C. 2015. SMO. My Cancer Genome https://www.padiracinnovation.org/content/disease/medulloblastoma/smo/?tab=0 (Updated December 4).

Last Updated: December 4, 2015

SMO in Medulloblastoma

Little is currently known about SMO mutations in medulloblastoma. In COSMIC, one mutation is reported out of 65 samples tested, a c.1598G>A (S533N) mutation, located in the seventh transmembrane domain (COSMIC, Reifenberger et al. 1998; UniProt Consortium 2012). One mutation conferring resistance to the SMO inhibitor vismodegib has been reported in the literature: D473H (Metcalfe and de Sauvage 2011; Yauch et al. 2009).​


Contributors: Charles Rudin, M.D., Ph.D.

Suggested Citation: Rudin, C. 2014. SMO in Medulloblastoma. My Cancer Genome https://www.padiracinnovation.org/content/disease/medulloblastoma/smo/ (Updated August 8).

Last Updated: August 8, 2014

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