ArticleStrahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]2021
FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro.
Article in Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al], 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Endothelial Cell pY397-FAK Expression Predicts the Risk of Breast Cancer Recurrences after Radiotherapy in the SweBCG91-RT Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Self-emulsifying Nano-PND oral delivery systems of PND1186: In silico modeling for bioavailability estimation.Journal of molecular liquids · 2025Article
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- Kinase inhibitors increase individual radiation sensitivity in normal cells of cancer patients.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2022Article
- Review
- The survival impact of palliative radiotherapy on synchronous metastatic pancreatic ductal adenocarcinoma: metastatic site can serve for radiotherapy-decision.Journal of Cancer · 2022Article
- Biological Hallmarks and New Therapeutic Approaches for the Treatment of PDAC.Life (Basel, Switzerland) · 2021Review
- Article
- PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation.Genes · 2021Article
- Desmoglein 3 contributes to tumorigenicity of pancreatic ductal adenocarcinoma through activating Src-FAK signaling.Animal cells and systems · 2021Article
- Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation.Frontiers in oncology · 2021Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionFocal adhesion kinase (FAK) is a nonreceptor tyrosine kinase protein frequently overexpressed in cancer and has been linked to an increase in the stem cell population of tumors, resistance to therapy, and metastatic spread. Pharmacological FAK inhibition in pancreatic cancer has received increased attention over the last few years, either alone or in combination with other therapeutics including chemotherapy and immunotherapy. However, its prognostic value and its role in radioresistance of pancreatic ducal adenocarcinoma (PDAC) is unknown. METHODS AND MATERIALS: Using the TCGA and GTEx databases, we investigated the genetic alterations and mRNA expression levels of PTK2 (the encoding-gene for FAK) in normal pancreatic tissue and pancreatic cancer and its impact on patient survival. Furthermore, we evaluated the expression of FAK and its tyrosine domain Ty-397 in three pancreatic cancer cell lines. We went further and evaluated the role of a commercial FAK tyrosine kinase inhibitor VS-4718 on the viability and radiosensitization of the pancreatic cell lines as well as its effect on the extracellular matrix (ECM) production from the pancreatic stellate cells. Furthermore, we tested the effect of combining radiation with VS-4718 in a three-dimensional (3D) multicellular pancreatic tumor spheroid model.
resultsA database analysis revealed a relevant increase in genetic alterations and mRNA expression of the PTK2 in PDAC, which were associated with lower progression-free survival. In vitro, there was only variation in the basal phosphorylation level of FAK in cell lines. VS-4718 radiosensitized pancreatic cell lines only in the presence of ECM-producing pancreatic stellate cells and markedly reduced the ECM production in the stromal cells. Finally, using a 3D multicellular tumor model, the combination of VS-4718 and radiotherapy significantly reduced the growth of tumor aggregates.
conclusionPharmacological inhibition of FAK in pancreatic cancer could be a novel therapeutic strategy as our results show a radiosensitization effect of VS-4718 in vitro in a multicellular 2D- and in a 3D-model of pancreatic cancer.
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