ArticleJournal of experimental & clinical cancer research : CR2021
Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Defactinib in Combination with Mitotane Can Be an Effective Treatment in Human Adrenocortical Carcinoma.International journal of molecular sciences · 2025Article
- Fibrotic Fortresses and Therapeutic Frontiers: Pancreatic Stellate Cells and the Extracellular Matrix in Pancreatic Cancer.Cancer medicine · 2025Review
- NJournal of experimental & clinical cancer research : CR · 2025Article
- Factors that determine cell fate in mitotically arrested cancer cells.Frontiers in cell and developmental biology · 2025Article
- Nanoarchitecting intelligently encapsulated designs for improved cancer therapy.Frontiers in bioengineering and biotechnology · 2025Review
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth.Journal of experimental & clinical cancer research : CR · 2023Article
- Barriers and opportunities for gemcitabine in pancreatic cancer therapy.American journal of physiology. Cell physiology · 2023Review
- HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2.Theranostics · 2023Article
- Synergism of FAK and ROS1 inhibitors in the treatment ofInternational journal of biological sciences · 2023Article
- Article
- Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy.Biochemical Society transactions · 2022Article
- Article
- New Pharmacological Strategies against Pancreatic Adenocarcinoma: The Multifunctional Thiosemicarbazone FA4.Molecules (Basel, Switzerland) · 2022Article
- Functional and clinical characteristics of focal adhesion kinases in cancer progression.Frontiers in cell and developmental biology · 2022Review
- A New Oxadiazole-Based Topsentin Derivative Modulates Cyclin-Dependent Kinase 1 Expression and Exerts Cytotoxic Effects on Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2021Article
- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.
methodsMass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway analysis and inferred kinase activity analysis was performed to identify novel targets. Subsequently, we investigated targeting of focal adhesion kinase (FAK) in vitro with drug perturbations in combination with chemotherapeutics used against PDAC. Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling. An orthotopic model of PDAC was used to evaluate the combination of defactinib with nab-paclitaxel.
resultsPDAC cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree. The non-receptor kinase, FAK, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis. Targeting of this kinase with defactinib validated reduced phosphorylation profiles. Additionally, FAK inhibition had anti-proliferative and anti-migratory effects. Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo.
conclusionsOur study shows high phosphorylation of several oncogenic receptor tyrosine kinases in PDAC cells and validated FAK inhibition as potential synergistic target with Nab-paclitaxel against this devastating disease.
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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.