ArticleCellular oncology (Dordrecht, Netherlands)2025
Pyrotinib inhibits the tumorigenicity of HER2-positive non-small cell lung cancer by inducing ARIH1/ubiquitin/lysosome-dependent degradation of HER2.
Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Cardiovascular Toxicity of Novel HER2-Targeted Agents and Multikinase Inhibitors in Oncology: From Mechanisms to Real-World Clinical Evidence.Pharmaceuticals (Basel, Switzerland) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
purposeNon-small cell lung cancer (NSCLC), accounting for the majority of lung cancer, is the leading cause of cancer death worldwide, and molecular targeted drugs promote greatly advance in the treatment of this disease. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in 1-5% of NSCLC cases, correlating with poorer outcomes and lack of approved targeted drugs. Pyrotinib is an irreversible HER2 receptor tyrosine kinase inhibitor developed for the treatment of HER2-positive advanced solid tumors; however, the comprehensive exploration of Pyrotinib's anti-tumor mechanism in HER2-positive NSCLC cells needs further explored.
methodsUsing HER2-high copy number NSCLC cancer cell lines, primary cells and subcutaneous tumor models in nude mice, we systematically evaluated pyrotinib’s anti-tumor activity through viability assays, Colony formation assay, and apoptosis analysis. Mechanistic studies included co-immunoprecipitation, Quantitative reverse transcription-PCR, ubiquitination assays, and Liquid Chromatography-Tandem Mass Spectrometry analysis.
resultsThis study revealed that Pyrotinib suppressed the tumorigenicity of HER2-positive NSCLC cells (H2170 and Calu-3 cell lines) by promoting HER2 degradation, inhibiting HER2 downstream signalings, inducing cell apoptosis, and ultimately triggering cell death. However, however, this drug presented low cytotoxic effects on H1299 (low-HER2 cell line) and BEAS-2B (human lung epithelial cell line) cells. Mechanistic analyses revealed that Pyrotinib facilitated HER2 degradation by inducing ubiquitination of HER2, enhancing interaction between ARIH1 and HER2, and subsequent triggering lysosomal degradation of HER2. Furthermore, Pyrotinib suppressed tumor growth of HER2-positive NSCLC xenografts, in an ARIH1-dependent manner.
conclusionPyrotinib enhances the binding of the E3 ubiquitin ligase ARIH1 to HER2, promoting HER2 ubiquitination and endocytosis, which leads to degradation via the lysosomal pathway. Our data explain why Pyrotinib has shown good efficacy in clinical trials and provide new insights into the application of Pyrotinib in HER2-positive non-small cell lung cancer. CLINICAL TRIAL NUMBER: Not applicable.
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.