Hedgehog pathway inhibitors
Pills that block a developmental signalling pathway hijacked by basal cell skin cancer, shrinking tumours that cannot be operated on; also used in some leukaemia.
Overview
Nearly all basal cell carcinomas have mutations activating the Hedgehog pathway through PTCH1 or SMO. Vismodegib (2012) and sonidegib (2015) inhibit SMO and produce responses in locally advanced and metastatic basal cell carcinoma, though muscle cramps, taste loss and hair loss lead many patients to stop. Glasdegib (2018) is approved with low-dose cytarabine in acute myeloid leukaemia. Resistance arises through SMO mutations and downstream activation.
How it works
Small molecules bind the transmembrane protein Smoothened, stopping activation of GLI transcription factors that drive proliferation.
- High response rates in advanced basal cell carcinoma
- Oral
- Neoadjuvant and intermittent regimens reduce toxicity
- Cramps, dysgeusia and alopecia cause discontinuation
- Teratogenic
- Acquired SMO resistance
Latest papers
topQuery for this technology: (TITLE:"Hedgehog pathway inhibitors" OR ABSTRACT:"Hedgehog pathway inhibitors") 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 Hedgehog pathway inhibitors, not a curated reading list.
Similar pages
not linked directly; found by shared links- TargetSmoothened (hedgehog pathway)
Shares Glasdegib, Sonidegib, Vismodegib, Basal cell carcinoma.
- PathwayBasal cell carcinoma (KEGG map)
Shares Sonidegib, Vismodegib, Hedgehog signalling, Basal cell carcinoma.
- PathwayFibroblast activation, desmoplasia & matrix stiffness
Shares Sonidegib, Vismodegib, Hedgehog signalling.
- PathwayProteoglycans in cancer
Shares Vismodegib, Hedgehog signalling.
- CancerSkin cancer (all types)
Shares Vismodegib, Basal cell carcinoma.