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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.
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.
Small molecules bind the transmembrane protein Smoothened, stopping activation of GLI transcription factors that drive proliferation.
Glasdegib is a hedgehog-pathway pill that, with low-dose chemotherapy, extends survival in older AML patients who cannot have intensive treatment; it has largely been displaced by venetoclax combinations.
Sonidegib (Odomzo) is the second hedgehog inhibitor for locally advanced basal cell carcinoma, similar in effect and side effects to vismodegib.
Vismodegib was the first hedgehog-pathway drug, for basal cell carcinomas too advanced for surgery; it shrinks most tumours but muscle cramps, taste loss and hair loss make long-term use hard.
Query 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.
Shares Glasdegib, PTCH1 (Patched 1), Patidegib gel in Gorlin syndrome (phase 2A), VISMONEO (vismodegib before surgery for locally advanced basal cell carcinoma).
Shares VISMONEO (vismodegib before surgery for locally advanced basal cell carcinoma), STEVIE (vismodegib in ordinary practice), BOLT, ERIVANCE BCC.
Shares PTCH1 (Patched 1), Patidegib gel in Gorlin syndrome (phase 2A), Sonidegib, Why people stop taking hedgehog inhibitors.
Shares PTCH1 (Patched 1), Sonidegib, BOLT, ERIVANCE BCC.
Shares Patidegib gel in Gorlin syndrome (phase 2A), STEVIE (vismodegib in ordinary practice), Why people stop taking hedgehog inhibitors, Locally advanced and metastatic basal cell carcinoma.
Shares Sonidegib, BOLT, Locally advanced and metastatic basal cell carcinoma.
Shares ERIVANCE BCC, Vismodegib, Locally advanced and metastatic basal cell carcinoma.
Shares Patidegib gel in Gorlin syndrome (phase 2A), Locally advanced and metastatic basal cell carcinoma, Basal cell carcinoma, Skin cancer (all types).