ArticleFrontiers in oncology2021
High Circulating Sonic Hedgehog Protein Is Associated With Poor Outcome in EGFR-Mutated Advanced NSCLC Treated With Tyrosine Kinase Inhibitors.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
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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.
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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
4 citing papers in PubMed, 5 citations in OpenAlex.
- Systemic Sonic Hedgehog Signaling Links Intestinal Nutrient Sensing With Sex-Specific Type 2 Diabetes Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Itraconazole Reversing Acquired Resistance to Osimertinib in NSCLC by Inhibiting the SHH/DUSP13B/p-STAT3 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unlocking the Potential of Biomarkers for Immune Checkpoint Inhibitors in Cancer Therapy.Cancers · 2023Article
- Targeting hedgehog-driven mechanisms of drug-resistant cancers.Frontiers in molecular biosciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionGrowing preclinical evidence has suggested that the Sonic hedgehog (Shh) pathway is involved in resistance to tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). However, little is known concerning the prognostic value of this pathway in this context. MATERIALS AND
methodsWe investigated the relationship between plasma levels of Shh and EGFRm NSCLC patients' outcome with EGFR TKIs. We included 74 consecutive patients from two institutions with EGFRm advanced NSCLC treated by EGFR TKI as first-line therapy. Plasma samples were collected longitudinally for each patient and were analyzed for the expression of Shh using an ELISA assay. The activation of the Shh-Gli1 pathway was assessed through immunohistochemistry (IHC) of Gli1 and RT-qPCR analysis of the transcripts of Gli1 target genes in 14 available tumor biopsies collected at diagnosis (baseline).
resultsAmong the 74 patients, only 61 had baseline (diagnosis) plasma samples, while only 49 patients had plasma samples at the first evaluation. Shh protein was detectable in all samples at diagnosis (
conclusionThese data support that higher levels of plasma Shh at diagnosis and increased levels of Shh along the course of the disease are related to the emergence of TKI resistance and poor outcome for EGFR-TKI therapy, suggesting that Shh levels could stand both as a prognostic and as a resistance biomarker for the management of
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