ArticleEBioMedicine2019
Integrin-linked kinase (ILK) and src homology 2 domain-containing phosphatase 2 (SHP2): Novel targets in EGFR-mutation positive non-small cell lung cancer (NSCLC).
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Prognostic significance of SHP2 (PTPN11) expression in solid tumors: A meta-analysis.PloS one · 2022Pooled it
- Plasma proteome-metabolome signatures enable non-invasive early detection and lymph node risk stratification in breast cancer.Molecular cancer · 2026Article
- Drug tolerance and persistence to EGFR inhibitor treatment are mediated by an ILK-SFK-YAP signaling axis in lung adenocarcinoma.Oncogene · 2025Article
- SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines.Frontiers in endocrinology · 2025Article
- PrPOncogene · 2024Article
- Overcoming MET-mediated resistance in oncogene-driven NSCLC.iScience · 2023Article
- Insights intoCancers · 2023Article
- Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.Toxicologic pathology · 2023Article
- Role of SHP2/PTPN11 in the occurrence and prognosis of cancer: A systematic review and meta-analysis.Oncology letters · 2023Article
- Therapeutic efficacy of the novel SHP2 degrader SHP2-D26, alone or in combination, against lung cancer is associated with modulation of p70S6K/S6, Bim and Mcl-1.Cancer gene therapy · 2022Article
- New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis.Cancers · 2022Article
- Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.International journal of molecular sciences · 2022Article
- Integrin-linked kinase (ILK): the known vs. the unknown and perspectives.Cellular and molecular life sciences : CMLS · 2022Review
- The Expression of PPAR Pathway-Related Genes Can Better Predict the Prognosis of Patients with Colon Adenocarcinoma.PPAR research · 2022Article
- Strategies to overcome drug resistance using SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Review
- High SHP2 expression determines the efficacy of PD-1/PD-L1 inhibitors in advanced KRAS mutant non-small cell lung cancer.Thoracic cancer · 2021Article
- Tumor immune microenvironment in epidermal growth factor receptor-mutated non-small cell lung cancer before and after epidermal growth factor receptor tyrosine kinase inhibitor treatment: a narrative review.Translational lung cancer research · 2021Review
- Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer.Nature communications · 2021Article
- Next-generation sequencing-based identification of EGFR and NOTCH2 complementary mutations in non-small cell lung cancer.Oncology letters · 2021Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe activation of multiple signaling pathways jeopardizes the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutation positive non-small cell lung cancer (NSCLC). Integrin-linked kinase (ILK) regulates the interactions between tumor cells and extracellular environment to activate signaling pathways and promote cell proliferation, migration, and epithelial-mesenchymal transition. Src homology 2 domain-containing phosphatase 2 (SHP2) is essential for receptor tyrosine kinase signaling and mitogen-activated protein kinase (MAPK) pathway activation.
methodsWe analyzed tumor ILK, β-receptor subunit glycoprotein 130 (gp130), SHP2, and stromal hepatocyte growth factor (HGF) and interleukin-6 (IL-6) mRNA expression in baseline tumor specimens of advanced EGFR-mutation positive NSCLC patients treated with EGFR TKIs.
resultsILK, when highly expressed, was an independent poor prognostic factor for the progression-free survival of the patients, both in the univariate (hazard ratio [HR for disease progression, 2.49; 95% CI, 1.37-4.52; P = .0020]) and in the multivariate (HR 3.74; 95% CI, 1.33-10.56; P = .0126) Cox regression model. Patients with high SHP2 expression had an almost 13-month shorter progression-free survival (P = .0094) and an 18-month shorter overall survival (P = .0182) in comparison to those with low SHP2 mRNA expression.
interpretationThe levels of ILK and SHP2 could be predictive for upfront combinatory therapy of EGFR TKIs plus SHP2 or ILK inhibitors. FUND: A grant from La Caixa Foundation, an Instituto de Salud Carlos III grant (RESPONSE, PIE16/00011), an Instituto de Salud Carlos III grant (PI14/01678), a Marie Skłodowska-Curie Innovative Training Networks European Grant (ELBA No 765492) and a Spanish Association Against Cancer (AECC) grant (PROYE18012ROSE).
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