ArticleOncotarget2015
Src inhibitors act through different mechanisms in Non-Small Cell Lung Cancer models depending on EGFR and RAS mutational status.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Progress on quinoline‑based antitumour agents: Mechanistic insights and optimization strategies (Review).Molecular medicine reports · 2026Review
- Retraction Note: Toll-like receptor 9 agonist IMO cooperates with everolimus in renal cell carcinoma by interfering with tumour growth and angiogenesis.British journal of cancer · 2025Article
- Src and Abl as Therapeutic Targets in Lung Cancer: Opportunities for Drug Repurposing.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A heterogeneous pharmaco-transcriptomic landscape induced by targeting a single oncogenic kinase.bioRxiv : the preprint server for biology · 2025Article
- Lung Cancer Therapy: The Role of Personalized Medicine.Cancers · 2025Review
- Dual Drug Repurposing: The Example of Saracatinib.International journal of molecular sciences · 2024Review
- A back-door insight into the modulation of Src kinase activity by the polyamine spermidine.eLife · 2023Article
- Peruvoside is a novel Src inhibitor that suppresses NSCLC cell growth and motility by downregulating multiple Src-EGFR-related pathways.American journal of cancer research · 2022Article
- CancerOmicsNet: a multi-omics network-based approach to anti-cancer drug profiling.Oncotarget · 2022Article
- N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition.International journal of molecular sciences · 2021Article
- RePhine: An Integrative Method for Identification of Drug Response-related Transcriptional Regulators.Genomics, proteomics & bioinformatics · 2021Article
- Standard of Care and Promising New Agents for the Treatment of Mesenchymal Triple-Negative Breast Cancer.Cancers · 2021Review
- Article
- Review
- A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control.Cell systems · 2020Article
- Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine.Journal of medicinal chemistry · 2020Article
- Targeting the Extra-Cellular Matrix-Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors.Frontiers in oncology · 2020Review
- Anti-vasospastic Effects of Epidermal Growth Factor Receptor Inhibitors After Subarachnoid Hemorrhage in Mice.Molecular neurobiology · 2019Article
- Article
- SRC and MEK Co-inhibition Synergistically Enhances the Anti-tumor Effect in Both Non-small-cell Lung Cancer (NSCLC) and Erlotinib-Resistant NSCLC.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, often related to Ras or secondary EGFR mutations, is a relevant clinical issue in Non-Small Cell Lung Cancer (NSCLC). Although Src TK has been involved in such resistance, clinical development of its inhibitors has been so far limited. To better define the molecular targets of the Src TKIs saracatinib, dasatinib and bosutinib, we used a variety of in vitro/in vivo studies. Kinase assays supported by docking analysis demonstrated that all the compounds directly inhibit EGFR TK variants. However, in live cells only saracatinib efficiently reduced EGFR activation, while dasatinib was the most effective agent in inhibiting Src TK. Consistently, a pronounced anti-proliferative effect was achieved with saracatinib, in EGFR mutant cells, or with dasatinib, in wt EGFR/Ras mutant cells, poorly dependent on EGFR and erlotinib-resistant. We then identified the most effective drug combinations to overcome resistance to EGFR inhibitors, both in vitro and in nude mice: in T790M EGFR erlotinib-resistant cells, saracatinib with the anti-EGFR mAb cetuximab; in Ras mutant erlotinib-resistant models, dasatinib with the MEK inhibitor selumetinib. Src inhibitors may act with different mechanisms in NSCLCs, depending on EGFR/Ras mutational profile, and may be integrated with EGFR or MEK inhibitors for different cohorts of NSCLCs.
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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.