biostudies-literatureJussila ARNCRR NIH HHSNCI NIH HHSNational Institutes of HealthNIAMS NIH HHSNIH HHS1368-1377.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC11116079biostudies-literatureUnknown144(6)Although basal cell carcinomas arise from ectopic Hedgehog pathway activation and can be treated with pathway inhibitors, sporadic basal cell carcinomas display high resistance rates, whereas tumors arising in patients with Gorlin syndrome with germline Patched (PTCH1) alterations are uniformly suppressed by inhibitor therapy. In rare cases, patients with Gorlin syndrome on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. In this study, we report a case of an SMO inhibitor-resistant tumor arising in a patient with Gorlin syndrome on suppressive SMO inhibitor for nearly a decade. Using a combination of multiomics and spatial transcriptomics, we define the tumor populations at the cellular anThe Journal of investigative dermatologyAcquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition.PMC11116079S10 RR025518S10RR027431-011R01AR04786S10 OD010580T32 AR007422T32AR007422-40R01 AR0467862R37ARO547801S10OD0105801F32CA254434P30 CA124435P30CA-0622035T32AR7422-37R37 AR054780P30 CA062203S10RR025518-01S10 RR027431F32 CA254434Oro AEHaensel DGaddam SJussila ARfalseAcquisition of Drug Resistance in Basal Cell Nevus Syndrome Tumors through Basal to Squamous Cell Carcinoma Transition.Although basal cell carcinomas arise from ectopic Hedgehog pathway activation and can be treated with pathway inhibitors, sporadic basal cell carcinomas display high resistance rates, whereas tumors arising in patients with Gorlin syndrome with germline Patched (PTCH1) alterations are uniformly suppressed by inhibitor therapy. In rare cases, patients with Gorlin syndrome on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. In this study, we report a case of an SMO inhibitor-resistant tumor arising in a patient with Gorlin syndrome on suppressive SMO inhibitor for nearly a decade. Using a combination of multiomics and spatial transcriptomics, we define the tumor populations at the cellular an2024-01-01T00:00:00Z2024 Jun2026-06-02T20:17:20.171Z2026-04-20T03:10:03.865ZS-EPMC111160793815793010.1016/j.jid.2023.10.040