ArticleMolecular cancer2015
Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Breed of origin analysis in genome-wide association studies: enhancing SNP-based insights into production traits in a commercial Brangus population.BMC genomics · 2024Article
- PRKCSH contributes to TNFSF resistance by extending IGF1R half-life and activation in lung cancer.Experimental & molecular medicine · 2024Article
- Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.JAMA network open · 2023Article
- Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.Molecular oncology · 2022Article
- Nintedanib and Dasatinib Treatments Induce Protective Autophagy as a Potential Resistance Mechanism in MPM Cells.Frontiers in cell and developmental biology · 2022Article
- Article
- IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK.Scientific reports · 2021Article
- Development of the phenylpyrazolo[3,4-Theranostics · 2021Article
- Chetomin, a Hsp90/HIF1α pathway inhibitor, effectively targets lung cancer stem cells and non-stem cells.Cancer biology & therapy · 2020Article
- PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis.Nature communications · 2020Article
- Review
- Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src.Molecules (Basel, Switzerland) · 2020Article
- Article
- MicroRNA-877 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting IGF-1R.Experimental and therapeutic medicine · 2019Article
- Article
- β-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer.Oncogene · 2018Article
- Src kinase inhibitor PP2 regulates the biological characteristics of A549 cells via the PI3K/Akt signaling pathway.Oncology letters · 2018Article
- Tescalcin/c-Src/IGF1Rβ-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1.Scientific reports · 2018Article
- FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion.Oncogene · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundTherapeutic interventions in the insulin-like growth factor receptor (IGF-1R) pathway were expected to provide clinical benefits; however, IGF-1R tyrosine kinase inhibitors (TKIs) have shown limited antitumor efficacy, and the mechanisms conveying resistance to these agents remain elusive.
methodsThe expression and activation of the IGF-1R and Src were assessed via the analysis of a publicly available dataset, as well as immunohistochemistry, Western blotting, RT-PCR, and in vitro kinase assays. The efficacy of IGF-1R TKIs alone or in combination with Src inhibitors was analyzed using MTT assays, colony formation assays, flow cytometric analysis, and xenograft tumor models.
resultsThe co-activation of IGF-1R and Src was observed in multiple human NSCLC cell lines as well as in a tissue microarray (n = 353). The IGF-1R and Src proteins mutually phosphorylate on their autophosphorylation sites. In high-pSrc-expressing NSCLC cells, linsitinib treatment initially inactivated the IGF-1R pathway but led a Src-dependent reactivation of downstream effectors. In low-pSrc-expressing NSCLC cells, linsitinib treatment decreased the turnover of the IGF-1R and Src proteins, ultimately amplifying the reciprocal co-activation of IGF-1R and Src. Co-targeting IGF-1R and Src significantly suppressed the proliferation and tumor growth of both high-pSrc-expressing and low-pSrc-expressing NSCLC cells in vitro and in vivo and the growth of patient-derived tissues in vivo.
conclusionsReciprocal activation between Src and IGF-1R occurs in NSCLC. Src causes IGF-1R TKI resistance by acting as a key downstream modulator of the cross-talk between multiple membrane receptors. Targeting Src is a clinically applicable strategy to overcome resistance to IGF-1R TKIs.
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