ArticleJCI insight2020
MEK activation modulates glycolysis and supports suppressive myeloid cells in TNBC.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- CD69 blockade restores the bone marrow niche and delays leukemogenesis in a mouse model ofCancer biology & therapy · 2026Article
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Emerging Therapeutic Landscapes for KRAS-Mutant Pancreatic Ductal Adenocarcinoma: Beyond the "Undruggable" Paradigm.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Review
- Spatiotemporal dynamics of tumor-associated neutrophils: bridging the gap between cancer progression and immunotherapy.Molecular cancer · 2026Review
- Decoding the tumor microenvironment of triple-negative breast cancer: from immune evasion to precision immunotherapy.Frontiers in immunology · 2026Review
- The chemokine network in triple-negative breast cancer: its role in immune microenvironment regulation, and prospects for targeted therapy.Frontiers in immunology · 2026Review
- A phase Ib/II trial of atezolizumab with cobimetinib or idasanutlin in metastatic estrogen receptor positive breast cancer.NPJ breast cancer · 2025Article
- Transcriptomic landscape of Hras12V oncogene-induced hepatocarcinogenesis with gender disparity.BMC cancer · 2025Article
- Yiai Fuzheng decoction inhibits triple-negative breast cancer by remodeling the immune microenvironment.Frontiers in immunology · 2025Article
- Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity.The Journal of clinical investigation · 2024Article
- Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review.Frontiers in immunology · 2024Review
- The role of metabolic reprogramming in immune escape of triple-negative breast cancer.Frontiers in immunology · 2024Review
- Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-β, and MAPK signaling pathways during breast tumor progression.Journal of translational medicine · 2023Review
- Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review.Biomedicines · 2023Review
- Oxidative phosphorylation inhibitors inhibit proliferation of endometriosis cells.Reproduction (Cambridge, England) · 2023Article
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- Regulation of DNA-PK activity promotes the progression of TNBC via enhancing the immunosuppressive function of myeloid-derived suppressor cells.Cancer medicine · 2023Article
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Direct Targeting of the Raf-MEK-ERK Signaling Cascade Inhibits Neuroblastoma Growth.Current oncology (Toronto, Ont.) · 2022Article
- Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 2 countries.
Funding
Abstract
Triple-negative breast cancers (TNBCs) are heterogeneous and aggressive, with high mortality rates. TNBCs frequently respond to chemotherapy, yet many patients develop chemoresistance. The molecular basis and roles for tumor cell-stromal crosstalk in establishing chemoresistance are complex and largely unclear. Here we report molecular studies of paired TNBC patient-derived xenografts (PDXs) established before and after the development of chemoresistance. Interestingly, the chemoresistant model acquired a distinct KRASQ61R mutation that activates K-Ras. The chemoresistant KRAS-mutant model showed gene expression and proteomic changes indicative of altered tumor cell metabolism. Specifically, KRAS-mutant PDXs exhibited increased redox ratios and decreased activation of AMPK, a protein involved in responding to metabolic homeostasis. Additionally, the chemoresistant model exhibited increased immunosuppression, including expression of CXCL1 and CXCL2, cytokines responsible for recruiting immunosuppressive leukocytes to tumors. Notably, chemoresistant KRAS-mutant tumors harbored increased numbers of granulocytic myeloid-derived suppressor cells (gMDSCs). Interestingly, previously established Ras/MAPK-associated gene expression signatures correlated with myeloid/neutrophil-recruiting CXCL1/2 expression and negatively with T cell-recruiting chemokines (CXCL9/10/11) across patients with TNBC, even in the absence of KRAS mutations. MEK inhibition induced tumor suppression in mice while reversing metabolic and immunosuppressive phenotypes, including chemokine production and gMDSC tumor recruitment in the chemoresistant KRAS-mutant tumors. These results suggest that Ras/MAPK pathway inhibitors may be effective in some breast cancer patients to reverse Ras/MAPK-driven tumor metabolism and immunosuppression, particularly in the setting of chemoresistance.
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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.