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The switch in the hedgehog developmental pathway that is stuck on in basal cell carcinoma and some medulloblastomas; three approved pills block it. This dossier gathers the 4 products (3 approved), 15 trials, 3 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Seven-transmembrane Frizzled-class receptor; cholesterol binding to its cysteine-rich domain and transmembrane site activates it once PTCH1 inhibition is relieved, translocating to the primary cilium and derepressing GLI2/3.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Basal cell carcinoma | 85% | hedgehog pathway activation (PTCH1 or SMO) | doi.org | |
| Medulloblastoma | 30% | SHH subgroup |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 |
|---|---|---|
| Small molecule 4 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Completed | A RANDOMIZED (1:1), DOUBLE-BLIND, MULTI-CENTER, PLACEBO CONTROLLED STUDY EVALUATING INTENSIVE CHEMOTHERAPY WITH OR WITHOUT GLASDEGIB (PF-04449913) OR AZACITIDINE (AZA) WITH OR WITHOUT GLASDEGIB IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA | - | ||
| 3 | Completed | A MULTI-CENTER CONTINUATION STUDY EVALUATING AZACITIDINE WITH OR WITHOUT GLASDEGIB (PF-04449913) IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA, MYELODYSPLASTIC SYNDROME OR CHRONIC MYELOMONOCYTIC LEUKEMIA | - | ||
| 3 | Completed | A Multicenter, Randomized, Double Blind, Vehicle-controlled, Phase 3 Efficacy and Safety Study of Patidegib Gel 2% for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Gorlin Syndrome | - | ||
| 3 | - | Randomized Phase-III Study to Compare Two Schedules of Gemtuzumab Ozogamicin as Adjunct to Intensive Induction Therapy and to Compare Intensive Postremission Therapy Double Blinded With or Without Glasdegib in Older Patients With Newly Diagnosed AML | - | ||
| 3 | Completed | Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study | - | ||
DETERMINE NCT05722886 | platform | Recruiting | Adults, teenagers and children in the United Kingdom with rare cancers, or common cancers carrying rare alterations, matched to licensed targeted drugs and immunotherapies outside their approved indications, with a route to NHS access for arms that work | Recruiting; no arm has reported. | |
Patidegib gel in Gorlin syndrome (phase 2A) NCT02762084 | 2 | Mixed | Gorlin syndrome, in which an inherited PTCH1 mutation drives continuous formation of new basal cell carcinomas: patidegib topical gel at 2 or 4 per cent against vehicle, applied twice daily to the whole face for six months, with the number of new surgically eligible basal cell carcinomas and hedgehog pathway signalling as the endpoints | Post hoc analyses in 17 participants suggested that patidegib topical gel reduced the number of new surgically eligible basal cell carcinomas and the level of hedgehog signalling, with minimal adverse effects; no pre-specified endpoint was met. | |
CUPISCO NCT03498521 | 2 | Positive | Newly diagnosed unfavourable cancer of unknown primary controlled by three cycles of platinum chemotherapy: randomised to molecularly guided therapy chosen from tissue and blood genomic profiling, or to continued chemotherapy | Median progression-free survival 6.1 months with molecularly guided therapy versus 4.4 months with continued chemotherapy (hazard ratio 0.72); overall survival immature. | |
| 2 | Positive | At least one histologically confirmed facial basal cell carcinoma, inoperable or operable only with a risk of functional loss or major disfigurement: oral vismodegib 150 mg daily for four to ten months before planned surgery, with the proportion of patients whose surgery was downstaged on a six-stage surgical classification as the primary endpoint | Surgical downstaging in 44 of 55 patients (80 per cent, 95 per cent confidence interval 67 to 90) with 27 complete responses, an objective response rate of 71 per cent, and recurrence in 16 of the 44 downstaged patients (36 per cent) by three years. | ||
MyPathway NCT02091141 | 2 | Completed | Advanced solid tumours with alterations in HER2, EGFR, BRAF, the Hedgehog pathway, ALK or high tumour mutational burden, outside the cancers for which the matching Roche drug is approved: trastuzumab with pertuzumab, erlotinib, vemurafenib with cobimetinib, vismodegib, alectinib or atezolizumab | Response in 23 percent of the first 230 patients; trastuzumab plus pertuzumab gave a 32 percent response rate in HER2-amplified colorectal cancer, now a guideline option; atezolizumab activity rose with tumour mutational burden. | |
STEVIE (vismodegib in ordinary practice) NCT01367665 | 2 | Mixed | Locally advanced or metastatic basal cell carcinoma in a population representative of clinical practice rather than of a pivotal trial: oral vismodegib 150 mg daily until progression, unacceptable toxicity or withdrawal, with safety as the primary objective | Investigator-assessed response 68.5 per cent in locally advanced and 36.9 per cent in metastatic basal cell carcinoma, with treatment-emergent adverse events in 98 per cent, serious events in 23.8 per cent and a median treatment duration of 8.6 months. | |
BOLT NCT01327053 | 2 | Positive | Locally advanced or metastatic basal cell carcinoma: sonidegib 200 mg versus 800 mg daily | Objective response at 200 mg: 43% in locally advanced and 15% in metastatic basal cell carcinoma (central review). | |
ERIVANCE BCC NCT00833417 | 2 | Positive | Locally advanced or metastatic basal cell carcinoma: vismodegib 150 mg daily | Objective response 43% in locally advanced and 30% in metastatic basal cell carcinoma (independent review). | |
SJMB12 NCT01878617 | 2 | Active | Newly diagnosed medulloblastoma aged 3 to 39, stratified by molecular subgroup and clinical risk: reduced craniospinal irradiation (15 Gy) for low-risk WNT tumours, vismodegib added for skeletally mature SHH tumours, and pemetrexed and gemcitabine added for intermediate- and high-risk group 3 and 4 tumours, with exercise and cognitive remediation randomisations | - | |
| 2 | Recruiting | A Phase 2 Study to Assess the Efficacy of SP-002 with Vismodegib for the Treatment of Locally Advanced Basal Cell Carcinoma | - |
No recorded escape route names this target.
KEGG's basal cell carcinoma map is the Hedgehog pathway: loss of the brake PTCH1 or activation of SMO leaves GLI transcription factors permanently on. Hedgehog inhibitors (vismodegib, sonidegib) shut this down in advanced disease.
Which nodes have drugs →Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.
Which nodes have drugs →This KEGG map shows how sugar-coated proteins on the cell surface and in the surrounding matrix (proteoglycans such as syndecans, glypicans, CD44 and decorin) catch growth factors and hand signals to receptors. It matters because these molecules set how loudly growth signals reach the tumour cell and how easily it invades.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"Smoothened" OR ABSTRACT:"Smoothened" OR TITLE:"hedgehog pathway" OR ABSTRACT:"hedgehog pathway" OR TITLE:"SMO" OR ABSTRACT:"SMO") 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 Smoothened (hedgehog pathway), not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/smoothened.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/smoothened.json. Licence CC BY-NC 4.0.