ArticleCancer cell2015
Smoothened variants explain the majority of drug resistance in basal cell carcinoma.
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
234 citing papers in PubMed, 3 syntheses or guidelines pooled it, 415 citations in OpenAlex.
- Prevalence of genetic alterations in basal cell carcinoma patients resistant to Hedgehog pathway inhibitors: a systematic review.Annals of medicine · 2025Pooled it
- S2k guideline basal cell carcinoma of the skin (update 2023).Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2024Guideline
- A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors.The oncologist · 2019Guideline
- Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Functional and therapeutic effects of Glabrescione B delivery by liposomes on Hedgehog-dependent tumors.Drug delivery and translational research · 2026Article
- Transforming Outcomes in Advanced Basal Cell Carcinoma: The Evolving Role of Systemic Therapy.American journal of clinical dermatology · 2026Review
- Article
- Sirt1 sustains Sonic hedgehog signaling to promote medulloblastoma progression through regulating Gli3 processing.Oncogene · 2026Article
- Decoding GPCR signaling reprogramming in cancer: molecular mechanisms and therapeutic implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Does Basal Cell Carcinoma Arise from a Precursor Lesion?The Journal of investigative dermatology · 2026Review
- Dissection of Gαs and Hedgehog Signaling Cross-talk Reveals Therapeutic Opportunities to Target Hedgehog-Dependent Tumors.Cancer research · 2026Article
- Aberrant Activation of the Hedgehog Pathway in Cutaneous Melanoma: Therapeutic Potential of Pharmacological Inhibitors.International journal of molecular sciences · 2026Article
- Clinical Outcomes of Sonidegib in Vismodegib-Exposed Locally Advanced Basal Cell Carcinoma: Insights From a Multicenter Descriptive Study.Journal of skin cancer · 2026Article
- Advances in Targeted and Immunotherapy for High-Risk Cutaneous Malignancies.Oncology research · 2026Review
- Resistance to SMO Inhibitors in Advanced Basal Cell Carcinoma: A Case Highlighting the Role of Molecular Tumor Profiling.International journal of molecular sciences · 2025Article
- In silico drug sensitivity predicts subgroup-specific therapeutics in medulloblastoma patients.Scientific reports · 2025Article
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
174 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here we identify SMO mutations in 50% (22 of 44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants conferring constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. In the presence of a SMO inhibitor, tumor cells containing either class of SMO mutants effectively outcompete cells containing the wild-type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.