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PTCH1 is the brake on the hedgehog growth pathway. When it is lost, as in nearly all basal cell carcinomas and in Gorlin syndrome, the pathway runs unchecked; vismodegib and sonidegib put the brake back one step down, at smoothened.
PTCH1 (chromosome 9q22.32) encodes Patched 1, the receptor for the hedgehog morphogens SHH, IHH and DHH and a negative regulator of smoothened: without hedgehog it acts as a cholesterol transporter that depletes cholesterol from the outer leaflet of the plasma membrane and so keeps SMO from being activated; hedgehog binding switches the transporter off and SMO signals (UniProt Q13635). The hedgehog pathway record states that PTCH1 loss or SMO mutation drives basal cell carcinoma (Gorlin syndrome) and the SHH subgroup of medulloblastoma. In OnCo, vismodegib and sonidegib treat the disease by inhibiting SMO downstream of PTCH1 loss, and germline PTCH1 loss in Gorlin syndrome is the population for the topical SMO inhibitor patidegib.
In plain words · PTCH1 is the brake on the hedgehog growth pathway. When it is lost, as in nearly all basal cell carcinomas and in Gorlin syndrome, the pathway runs unchecked; vismodegib and sonidegib put the brake back one step down, at smoothened.
PTCH1 is the brake on the hedgehog growth pathway. When it is lost, as in nearly all basal cell carcinomas and in Gorlin syndrome, the pathway runs unchecked; vismodegib and sonidegib put the brake back one step down, at smoothened.
A tumour suppressor rather than a druggable target: PTCH1 inactivation is what makes a tumour hedgehog-dependent and so eligible for SMO antagonists.
No product in this corpus aims at PTCH1 (Patched 1) yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1996. Earliest sequence paper UniProt cites for the protein: Johnson R.L. et al, Science, 1996, "Human homolog of patched, a candidate gene for the basal cell nevus syndrome". Source.
A tumour suppressor rather than a druggable target: PTCH1 inactivation is what makes a tumour hedgehog-dependent and so eligible for SMO antagonists. The hedgehog pathway record notes resistance through SMO mutations or SUFU and GLI2 alterations downstream.
Query for this target: (TITLE:"PTCH1" OR ABSTRACT:"PTCH1" OR TITLE:"Patched 1" OR ABSTRACT:"Patched 1" OR TITLE:"PTCH" OR ABSTRACT:"PTCH" OR TITLE:"NBCCS" OR ABSTRACT:"NBCCS" OR TITLE:"patched 1" OR ABSTRACT:"patched 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PTCH1 (Patched 1), not a curated reading list.
Shares Patidegib, Sonidegib, Hedgehog pathway inhibitors, Smoothened (hedgehog pathway).
Shares Hedgehog pathway inhibitors, Vismodegib, Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma.
Shares Hedgehog pathway inhibitors, Smoothened (hedgehog pathway), Vismodegib, Hedgehog signalling.
Shares Hedgehog pathway inhibitors, Basal cell carcinoma (KEGG map), Smoothened (hedgehog pathway), Vismodegib.
Shares Patidegib, Hedgehog pathway inhibitors, Smoothened (hedgehog pathway), Hedgehog signalling.
Shares Sonidegib, Hedgehog pathway inhibitors, Basal cell carcinoma (KEGG map), Smoothened (hedgehog pathway).
Shares Hedgehog pathway inhibitors, Smoothened (hedgehog pathway), Vismodegib, Hedgehog signalling.
Shares Patidegib, Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma.