PTCH1 (Patched 1)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
A tumour suppressor rather than a druggable target: PTCH1 inactivation is what makes a tumour hedgehog-dependent and so eligible for SMO antagonists.
- 3 · How drugs use it
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).
External identifiers
Biology
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.
- Basal cell carcinoma (PTCH1 loss in nearly all cases)
- SHH-subgroup medulloblastoma
- Gorlin (basal cell nevus) syndrome (germline PTCH1 loss)
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery 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.
Similar pages
not linked directly; found by shared links- TrialERIVANCE BCC
Shares Hedgehog pathway inhibitors, Basal cell carcinoma (KEGG map), Smoothened (hedgehog pathway), Hedgehog signalling.
- TrialBOLT
Shares Hedgehog pathway inhibitors, Basal cell carcinoma (KEGG map), Sonidegib, Smoothened (hedgehog pathway).
- TrialTo Assess the Safety and Efficacy of SP-002 with Vismodegib for the Treatment of Locally Advanced Basal Cell Carcinoma
Shares Hedgehog pathway inhibitors, Vismodegib, Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma.
- TrialEfficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome
Shares Patidegib, Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma.
- TreatmentGlasdegib
Shares Hedgehog pathway inhibitors, Smoothened (hedgehog pathway).
- TrialClinical Trial to Evaluate BO-112 in Patients With Basal Cell Carcinoma (BCC)
Shares Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma.
- TermMedulloblastoma molecular groups (WNT, SHH, group 3, group 4)
Shares Sonidegib, Vismodegib, SHH-activated medulloblastoma.
- Key paperBOLT: two doses of sonidegib in locally advanced or metastatic basal cell carcinoma
Shares Sonidegib, Locally advanced and metastatic basal cell carcinoma.