ArticleNature cancer2022
Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 102 citations in OpenAlex.
- First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.Signal transduction and targeted therapy · 2024Trial
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- Article
- Nintedanib inhibits the VEGFR-ERK signaling pathway in human KRAS-mutated cancer cells.Cell death & disease · 2026Article
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- High-quality acinar cell isolation enables single-cell analysis of healthy and injured pancreas.Cell reports methods · 2026Article
- Identification of PRRG1 as a possible molecular target of pancreatic cancer.Cell death & disease · 2026Article
- The mechanisms and clinical prospects of combining chemotherapy with immunotherapy for advanced pancreatic cancer.Discover oncology · 2026Review
- Identification of HSPE1 as a new actionable cancer vulnerability leads to an innovative and effective combination therapy for pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.Cell reports. Medicine · 2026Article
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- Enteric neuro-immune-tumor ecosystem in pancreatic, colorectal, and gastric malignancies: context dependence and translational priorities.Frontiers in immunology · 2026Review
- Nanorobots hold PD-L1 and break membrane of colorectal cancer cells for immunotherapy.Nature nanotechnology · 2026Article
- First Report of Trametinib-Nintedanib Combination in KRAS G12D-Mutated Pancreatic Cancer: Efficacy and Fatal Hemorrhagic Complication: A Case Report.Clinical case reports · 2025Article
- Pan-ERBB Inhibitors Synergize With KRAS Inhibitors in Rectal Cancer.United European gastroenterology journal · 2025Article
- A Phase IB Study of Binimetinib and Palbociclib in Molecularly Selected Advanced Triple-Negative Breast Cancer.Cancer research communications · 2025Article
- Importance of landscape exploration and progress in molecular therapies and precision medicine for pancreatic ductal adenocarcinoma.World journal of gastrointestinal oncology · 2025Review
- Hypoxia- and lactate metabolism-associated prognostic and therapeutic signature in pancreatic cancer.Discover oncology · 2025Article
- Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.Nature biomedical engineering · 2025Article
- KRASMolecular oncology · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
37 authors at 7 institutions in 1 country.
Funding
Abstract
KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted and immunotherapies. Among the different PDAC subtypes, basal-like mesenchymal PDAC, which is driven by allelic imbalance, increased gene dosage and subsequent high expression levels of oncogenic KRAS, shows the most aggressive phenotype and strongest therapy resistance. In the present study, we performed a systematic high-throughput combination drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi-kinase inhibitor nintedanib, which targets KRAS-directed oncogenic signaling in mesenchymal PDAC. This combination treatment induces cell-cycle arrest and cell death, and initiates a context-dependent remodeling of the immunosuppressive cancer cell secretome. Using a combination of single-cell RNA-sequencing, CRISPR screens and immunophenotyping, we show that this combination therapy promotes intratumor infiltration of cytotoxic and effector T cells, which sensitizes mesenchymal PDAC to PD-L1 immune checkpoint inhibition. Overall, our results open new avenues to target this aggressive and therapy-refractory mesenchymal PDAC subtype.
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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.