ArticleProceedings of the National Academy of Sciences of the United States of America2013
Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF-induced neutrophil recruitment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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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
69 citing papers in PubMed, 112 citations in OpenAlex.
- Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- New Insights Into the Role of Neutrophils in Lymphoma.Cancer medicine · 2026Review
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Tumor-associated neutrophils in pancreatic ductal adenocarcinoma: mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Review
- Immunosuppressive tumor microenvironment in pancreatic cancer: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
- Celebrating the 1945 JNCI pioneering contribution to antiangiogenic therapy for cancer.Journal of the National Cancer Institute · 2024Article
- Review
- Changes in cell morphology and function induced by the NRAS Q61R mutation in lymphatic endothelial cells.PloS one · 2024Article
- Immune Evasion of G-CSF and GM-CSF in Lung Cancer.Tuberculosis and respiratory diseases · 2024Article
- Adenosquamous carcinoma of the gallbladder simultaneously producing granulocyte-colony-stimulating factor and parathyroid hormone-related protein.Clinical journal of gastroenterology · 2023Article
- Targeting angiogenesis in oncology, ophthalmology and beyond.Nature reviews. Drug discovery · 2023Review
- Xuanhusuo powder has an anti-breast cancer effect by inhibiting myeloid-derived suppressor cell differentiation in the spleen of mice through down-regulating granulocyte colony stimulating factor.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Oral squamous cell carcinoma cell-derived GM-CSF regulates PD-L1 expression in tumor-associated macrophages through the JAK2/STAT3 signaling pathway.American journal of cancer research · 2023Article
- [Paraneoplastic hyperleukocytosis in lung cancer].Innere Medizin (Heidelberg, Germany) · 2022Article
- Inhibition of IRAK1 Is an Effective Therapy for Autoimmune Hypophysitis in Mice.International journal of molecular sciences · 2022Article
- Tumor accomplice: T cell exhaustion induced by chronic inflammation.Frontiers in immunology · 2022Review
- Article
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
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b(+)Gr1(+) myeloid cells and has been implicated in resistance to anti-VEGF therapy in mouse models. High G-CSF production has been associated with a poor prognosis in cancer patients. Here we show that activation of the RAS/MEK/ERK pathway regulates G-CSF expression through the Ets transcription factor. Several growth factors induced G-CSF expression by a MEK-dependent mechanism. Inhibition of G-CSF release with a MEK inhibitor markedly reduced G-CSF production in vitro and synergized with anti-VEGF antibodies to reduce CD11b(+)Ly6G(+) neutrophil mobilization and tumor growth and led to increased survival in animal models of cancer, including a genetically engineered mouse model of pancreatic adenocarcinoma. Analysis of biopsies from pancreatic cancer patients revealed increased phospho-MEK, G-CSF, and Ets expression and enhanced neutrophil recruitment compared with normal pancreata. These results provide insights into G-CSF regulation and on the mechanism of action of MEK inhibitors and point to unique anticancer strategies.
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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.