ArticleCancer research2015
RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.International journal of molecular sciences · 2021Pooled it
- Pathological Insights into the Limitations of Clinical and Dermoscopic Evaluations in Monitoring Sonidegib Treatment Response for Locally Advanced Basal Cell Carcinoma: A Real-World Study.Dermatology and therapy · 2026Article
- Disproportionality analysis comparing safety profiles of sonidegib and vismodegib based on the FAERS database.Scientific reports · 2025Article
- SMARCA5 is required for the development of granule cell neuron precursors and Sonic Hedgehog Medulloblastoma growth.Scientific reports · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Evaluation of Benzo[cd]indol-2(1H)-ones as Downstream Hedgehog Pathway Inhibitors.ChemistryOpen · 2025Article
- Research progress on the pathogenesis, clinical impact, and traditional Chinese medicine treatment of polycystic ovary syndrome complicated by insulin resistance.Frontiers in pharmacology · 2025Review
- Adverse events associated with vismodegib: insights from a real-world pharmacovigilance study using the FAERS database.Frontiers in pharmacology · 2025Article
- Review
- Ezh2 Delays Activation of Differentiation Genes During Normal Cerebellar Granule Neuron Development and in Medulloblastoma.bioRxiv : the preprint server for biology · 2024Article
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma.JID innovations : skin science from molecules to population health · 2024Article
- A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma.Cell reports · 2024Article
- Genome-wide CRISPR-Cas9 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma.Acta neuropathologica communications · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies.Cancers · 2024Review
- TheInternational journal of molecular sciences · 2024Article
- A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.Cancer research · 2024Article
- SALL4 is a CRL3Cell death and differentiation · 2024Article
- Cross-species analysis of SHH medulloblastoma models reveals significant inhibitory effects of trametinib on tumor progression.Cell death discovery · 2023Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Aberrant Shh signaling promotes tumor growth in diverse cancers. The importance of Shh signaling is particularly evident in medulloblastoma and basal cell carcinoma (BCC), where inhibitors targeting the Shh pathway component Smoothened (Smo) show great therapeutic promise. However, the emergence of drug resistance limits long-term efficacy, and the mechanisms of resistance remain poorly understood. Using new medulloblastoma models, we identify two distinct paradigms of resistance to Smo inhibition. Sufu mutations lead to maintenance of the Shh pathway in the presence of Smo inhibitors. Alternatively activation of the RAS-MAPK pathway circumvents Shh pathway dependency, drives tumor growth, and enhances metastatic behavior. Strikingly, in BCC patients treated with Smo inhibitor, squamous cell cancers with RAS/MAPK activation emerged from the antecedent BCC tumors. Together, these findings reveal a critical role of the RAS-MAPK pathway in drug resistance and tumor evolution of Shh pathway-dependent tumors.
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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.