{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:40:23Z","timestamp":1790764823790,"version":"4.1.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"PellePharm, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with Gorlin (basal cell naevus) syndrome (GS) have numerous phenotypic abnormalities due to overactivity of the hedgehog (HH) signalling pathway, most commonly caused by a heritable mutation in PTCH1, which encodes a major inhibitor of this pathway. Oral HH inhibitors (HHi) can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit\u2013risk ratio, we developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop oral HHi treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To determine whether or not patidegib topical gel 2% or 4% can accumulate in high enough concentrations to have local anti-BCC efficacy but not so high that systemic drug levels produce the adverse effects typical of oral HHi treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a small randomized double-blinded phase IIA trial at two sites in the UK, to assess the clinical and molecular efficacy and adverse effects of 6\u2005months of twice-daily application of patidegib topical gel to the entire face, as well as to treatment-targeted surgically eligible BCCs at other anatomical sites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Post hoc analyses suggested that patidegib topical gel reduced the number of new, surgically eligible BCCs and the level of HH signalling, with minimal adverse effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patidegib topical gel warrants further clinical development.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae444","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T11:24:56Z","timestamp":1731669896000},"page":"611-617","source":"Crossref","is-referenced-by-count":10,"title":["Topical application of the Hedgehog inhibitor patidegib in\u00a0patients with Gorlin syndrome: a phase II trial"],"prefix":"10.1093","volume":"192","author":[{"given":"John T","family":"Lear","sequence":"first","affiliation":[{"name":"Department of Dermatology, Manchester Royal Infirmary , Manchester ,","place":["UK"]},{"name":"Manchester Academic Health Science Centre, University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A","family":"Harwood","sequence":"additional","affiliation":[{"name":"Royal London Hospital, Barts Health NHS Trust\/Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshaan","family":"Hasan","sequence":"additional","affiliation":[{"name":"Royal London Hospital, Barts Health NHS Trust\/Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Kentley","sequence":"additional","affiliation":[{"name":"Royal London Hospital, Barts Health NHS Trust\/Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Thomson","sequence":"additional","affiliation":[{"name":"Royal London Hospital, Barts Health NHS Trust\/Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Manchester Royal Infirmary , Manchester ,","place":["UK"]},{"name":"Manchester Academic Health Science Centre, University of Manchester , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Alderman","sequence":"additional","affiliation":[{"name":"PellePharm, Inc. , San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"DeSouza","sequence":"additional","affiliation":[{"name":"PellePharm, Inc. , San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Ervin H","family":"Epstein","sequence":"additional","affiliation":[{"name":"PellePharm, Inc. , San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2045-4151","authenticated-orcid":false,"given":"Gerd G","family":"Kochendoerfer","sequence":"additional","affiliation":[{"name":"PellePharm, Inc. , San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Y","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Stanford University School of Medicine , Stanford, CA 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adult patients with solid tumors","volume":"19","author":"Jimeno","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2025031819360595700_ljae444-B10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/(SICI)1096-8628(19970331)69:3<299::AID-AJMG16>3.0.CO;2-M","article-title":"Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome","volume":"69","author":"Kimonis","year":"1997","journal-title":"Am J Med Genet"},{"key":"2025031819360595700_ljae444-B11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejca.2019.06.003","article-title":"Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines","volume":"118","author":"Peris","year":"2019","journal-title":"Eur J Cancer"},{"key":"2025031819360595700_ljae444-B12","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/jid.2011.48","article-title":"Topical treatment of basal cell carcinomas in nevoid basal cell carcinoma syndrome 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