ArticleProceedings of the National Academy of Sciences of the United States of America2023
KRAS mutation-driven angiopoietin 2 bestows anti-VEGF resistance in epithelial carcinomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 13 citations in OpenAlex.
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- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Enhancing CAR-T Cell Efficacy in Solid Tumors by Inhibiting CCL5/VEGF-Mediated Angiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Plasma Biomarkers Associated with Clinical Outcomes of FOLFIRI Plus Ramucirumab in RAS Wild-Type Metastatic Colorectal Cancer: The JACCRO CC-16AR Trial.Targeted oncology · 2026Article
- Nintedanib inhibits the VEGFR-ERK signaling pathway in human KRAS-mutated cancer cells.Cell death & disease · 2026Article
- Mechanisms of Pericyte-Mediated Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- New hybrid pyridine-1,2,4-triazole scaffolds: synthesis, in vitro evaluation of anticancer and antimicrobial activity, and in silico insights.Scientific reports · 2026Article
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- Research Progress Regarding the Use of Single-Cell Sequencing Technology in Analyzing Tumor Endothelial Cell Pathophysiology.International journal of molecular sciences · 2025Review
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- Convergent inducers and effectors of T cell paralysis in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Combination of vascular surgery with novel vascular targeting agents as cancer therapeutics.Frontiers in oncology · 2025Review
- Mechanistic studies and therapeutic potential of angiopoietin in head and neck tumor angiogenesis.Frontiers in oncology · 2025Review
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
- The possible dual role of Ang-2 in the prognosis of pancreatic cancer.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Defining reliable surrogate markers and overcoming drug resistance are the most challenging issues for improving therapeutic outcomes of antiangiogenic drugs (AADs) in cancer patients. At the time of this writing, no biomarkers are clinically available to predict AAD therapeutic benefits and drug resistance. Here, we uncovered a unique mechanism of AAD resistance in epithelial carcinomas with KRAS mutations that targeted angiopoietin 2 (ANG2) to circumvent antivascular endothelial growth factor (anti-VEGF) responses. Mechanistically, KRAS mutations up-regulated the FOXC2 transcription factor that directly elevated ANG2 expression at the transcriptional level. ANG2 bestowed anti-VEGF resistance as an alternative pathway to augment VEGF-independent tumor angiogenesis. Most colorectal and pancreatic cancers with KRAS mutations were intrinsically resistant to monotherapies of anti-VEGF or anti-ANG2 drugs. However, combination therapy with anti-VEGF and anti-ANG2 drugs produced synergistic and potent anticancer effects in KRAS-mutated cancers. Together, these data demonstrate that KRAS mutations in tumors serve as a predictive marker for anti-VEGF resistance and are susceptible to combination therapy with anti-VEGF and anti-ANG2 drugs.
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