ArticleBreast cancer research : BCR2014
Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models.
Article in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 41 papers.
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41 citing papers in PubMed, 66 citations in OpenAlex.
- Selective antitumor and apoptosis‑inducing effects of the Src inhibitor PP1 in human tongue squamous cell carcinoma cells.International journal of oncology · 2026Article
- Berberine: a promising strategy to combat cetuximab-resistance in colorectal cancer.BMC cancer · 2025Article
- EGFR-to-Src family tyrosine kinase switching in proliferating-DTP TNBC cells creates a hyperphosphorylation-dependent vulnerability to EGFR TKI.Cancer cell international · 2025Article
- Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.Translational oncology · 2024Article
- Structural Basis for Long Residence Time c-Src Antagonist: Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2024Article
- YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer.Archives of toxicology · 2024Article
- Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.Molecular oncology · 2022Article
- An overview of resistance to Human epidermal growth factor receptor 2 (Her2) targeted therapies in breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Tyrosine Kinase Inhibitors Are Promising Therapeutic Tools for Cats with HER2-Positive Mammary Carcinoma.Pharmaceutics · 2021Article
- Article
- Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels.Investigational new drugs · 2021Article
- Adipocyte-conditioned medium induces resistance of breast cancer cells to lapatinib.BMC pharmacology & toxicology · 2020Article
- Review
- Bioengineered scaffolds for 3D culture demonstrate extracellular matrix-mediated mechanisms of chemotherapy resistance in glioblastoma.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Targeted lapatinib anti-HER2/ErbB2 therapy resistance in breast cancer: opportunities to overcome a difficult problem.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Synergistic effect of STAT3‑targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo.Molecular medicine reports · 2019Article
- Dasatinib Treatment Increases Sensitivity to c-Met Inhibition in Triple-Negative Breast Cancer Cells.Cancers · 2019Article
- Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer.Nature communications · 2019Article
- The Importance of the Right Framework: Mitogen-Activated Protein Kinase Pathway and the Scaffolding Protein PTPIP51.International journal of molecular sciences · 2018Review
- A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance.Integrative biology : quantitative biosciences from nano to macro · 2017Article
Corrections and comments
- Retracted
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSrc tyrosine kinase overactivation has been correlated with a poor response to human epidermal growth factor receptor 2 (HER2) inhibitors in breast cancer. To identify the mechanism by which Src overexpression sustains this resistance, we tested a panel of breast cancer cell lines either sensitive or resistant to lapatinib.
methodsTo determine the role of Src in lapatinib resistance, we evaluated the effects of Src inhibition/silencing in vitro on survival, migration, and invasion of lapatinib-resistant cells. In vivo experiments were performed in JIMT-1 lapatinib-resistant cells orthotopically implanted in nude mice. We used artificial metastasis assays to evaluate the effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Src-dependent signal transduction was investigated with Western blot and ELISA analyses.
resultsSrc activation was higher in lapatinib-resistant than in lapatinib-sensitive cells. The selective small-molecule Src inhibitor saracatinib combined with lapatinib synergistically inhibited the proliferation, migration, and invasion of lapatinib-resistant cells. Saracatinib combined with lapatinib significantly prolonged survival of JIMT-1-xenografted mice compared with saracatinib alone, and impaired the formation of lung metastases. Unexpectedly, in lapatinib-resistant cells, Src preferentially interacted with epidermal growth factor receptor (EGFR) rather than with HER2. Moreover, EGFR targeting and lapatinib synergistically inhibited survival, migration, and invasion of resistant cells, thereby counteracting Src-mediated resistance. These findings demonstrate that Src activation in lapatinib-resistant cells depends on EGFR-dependent rather than on HER2-dependent signaling.
conclusionsComplete pharmacologic EGFR/HER2 inhibition is required to reverse Src-dependent resistance to lapatinib in breast cancer.
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