ArticleCancer discovery2022
Stromal Reprogramming by FAK Inhibition Overcomes Radiation Resistance to Allow for Immune Priming and Response to Checkpoint Blockade.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04331041 (Phase II Study of Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma), which is not on this map. Cited by 69 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Phase II Study of Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma
Who cites it
69 citing papers in PubMed, 100 citations in OpenAlex.
- Neoadjuvant BMS-813160, Nivolumab, Gemcitabine, and Nab-Paclitaxel for Patients with Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- 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
- Tumor FAK supports fibrillar collagen expression in ovarian cancer ascites.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway.iScience · 2026Article
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- From force to fate: Implications of mechanomemory in lung disease.Respiratory research · 2026Review
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Stromal homeostasis-restoring "rocket-like" nanomedicine inhibited pancreatic tumor growth in vivo.Materials today. Bio · 2026Article
- Arp2/3 complex and β1 integrin drive an invasive front through extracellular matrix adaptation in pancreatic cancer.International journal of cancer · 2026Article
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- UNC5B activates hepatic stellate cells and promotes liver fibrosis via FAK.Cell communication and signaling : CCS · 2026Article
- Serial Thermal Ablation Induces Abscopal Antitumor Immunity and Reveals Targetable CSF1R-Dependent Resistance in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- Immune Stromal Components Impede Biological Effectiveness of Carbon Ion Therapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma.Molecular cancer therapeutics · 2026Article
- Bracing for the storm: emerging resistance mechanisms to KRAS inhibitors in pancreatic cancer and strategies to overcome them.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Engineered cyclic peptide targeting ITGA5 disrupts tumor-stroma interaction to overcome desmoplasia and resistance in pancreatic ductal adenocarcinoma.Acta pharmaceutica Sinica. B · 2026Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
The effects of radiotherapy (RT) on tumor immunity in pancreatic ductal adenocarcinoma (PDAC) are not well understood. To better understand if RT can prime antigen-specific T-cell responses, we analyzed human PDAC tissues and mouse models. In both settings, there was little evidence of RT-induced T-cell priming. Using in vitro systems, we found that tumor-stromal components, including fibroblasts and collagen, cooperate to blunt RT efficacy and impair RT-induced interferon signaling. Focal adhesion kinase (FAK) inhibition rescued RT efficacy in vitro and in vivo, leading to tumor regression, T-cell priming, and enhanced long-term survival in PDAC mouse models. Based on these data, we initiated a clinical trial of defactinib in combination with stereotactic body RT in patients with PDAC (NCT04331041). Analysis of PDAC tissues from these patients showed stromal reprogramming mirroring our findings in genetically engineered mouse models. Finally, the addition of checkpoint immunotherapy to RT and FAK inhibition in animal models led to complete tumor regression and long-term survival. SIGNIFICANCE: Checkpoint immunotherapeutics have not been effective in PDAC, even when combined with RT. One possible explanation is that RT fails to prime T-cell responses in PDAC. Here, we show that FAK inhibition allows RT to prime tumor immunity and unlock responsiveness to checkpoint immunotherapy. This article is highlighted in the In This Issue feature, p. 2711.
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Registered trials
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.