ArticleJournal of experimental & clinical cancer research : CR2022
Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Zebrafish tumor xenograft models for drug-screening: a systematic review of methods for treatment assessment.Journal of translational medicine · 2026Pooled it
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Inflammatory bowel disease and breast cancer: epidemiological evidence, shared biology, and clinical management.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Integrated bioinformatics analyses for GSDMB in carcinogenesis and progression of bladder cancer.Translational andrology and urology · 2026Article
- Downregulation of GSDMB by EBV-encoded miR-BART12-3p suppresses killer lymphocyte-mediated pyroptosis in gastric cancer cells.PLoS pathogens · 2026Article
- Review
- The Role of Gasdermin B-Mediated Pyroptosis in Bladder Cancer Diagnosis.International journal of molecular sciences · 2026Article
- Pyroptosis Regulated by N6-Methyladenosine Modification: Implications for Pyroptosis-Related Disease Therapy.Journal of innate immunity · 2026Review
- Profiling the Complexity of Resistance Factors in Cancer Cells Towards Berberine and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- The Histone Deacetylase Inhibitor Entinostat Mediates HER2 Downregulation in Gastric Cancer, Providing the Basis for Its Particular Efficacy in HER2-Amplified Tumors and in Combination Therapies.Cancer research and treatment · 2025Article
- Functional Materials Targeted Regulation of Gasdermins: From Fundamentals to Functionalities and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The novel BCL-2/BCL-XL inhibitor APG-1252-mediated cleavage of GSDME enhances the antitumor efficacy of HER2-targeted therapy in HER2-positive gastric cancer.Acta pharmacologica Sinica · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- eIF3b-driven autophagy and Wnt/β-catenin crosstalk: a novel regulatory axis in adriamycin resistance of breast cancer.Oncology reviews · 2025Review
- Target fishing: from "needle in haystack" to "precise guidance"--new technology, new strategy and new opportunity.Frontiers in pharmacology · 2025Review
- Review
- The role of pyroptosis in cancer: key components and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Let's make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment.Cell biology and toxicology · 2024Review
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 1 country.
Funding
Abstract
backgroundGasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors.
methodsDifferent in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples.
resultsGSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers.
conclusionOur findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome.
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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.