ArticleThe Journal of experimental medicine2018
Therapeutically targeting tumor microenvironment-mediated drug resistance in estrogen receptor-positive breast cancer.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Cancer signaling networks in tumor progression and drug resistance: Crosstalk, adaptive reprogramming and therapeutic targeting (Review).Oncology reports · 2026Review
- CAFs and Endocrine Therapy Resistance in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2026Review
- Unlocking the Therapeutic Potential of Integrin-Linked Kinase Inhibitors in Bioengineered 3D Breast Tumor Stroma Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Bone Metastasis in Estrogen Receptor-Positive Breast Cancer: Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2026Review
- Reprogramming the immunosuppressive breast cancer microenvironment: integrating cellular, metabolic, and stromal targets for rational immunotherapy.Frontiers in immunology · 2026Review
- Single-cell and spatial transcriptomics reveal P4HA2-mediated radiotherapy resistance mechanisms in breast cancer.Theranostics · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Comparative Analysis of Chemotherapy Resistance Mechanisms in Humans and Companion Animals.Veterinary sciences · 2025Review
- Mechanisms of tumor-associated macrophages in breast cancer and treatment strategy.Frontiers in immunology · 2025Review
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- Review
- Overcoming drug resistance of cancer cells by targeting the FGF1/FGFR1 axis with honokiol or FGF ligand trap.Frontiers in pharmacology · 2024Article
- Ligand-based active targeting strategies for cancer theranostics.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Cancer Stem Cells and the Tumor Microenvironment in Tumor Drug Resistance.Stem cell reviews and reports · 2023Review
- Review
- Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment.Frontiers in oncology · 2023Review
- Molecular interaction of metastasis suppressor genes and tumor microenvironment in breast cancer.Exploration of targeted anti-tumor therapy · 2023Review
- Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update.Frontiers in endocrinology · 2023Review
- Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role.Therapeutic advances in medical oncology · 2022Review
- FGFR signaling and endocrine resistance in breast cancer: Challenges for the clinical development of FGFR inhibitors.Biochimica et biophysica acta. Reviews on cancer · 2021Review
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 at 5 institutions in 2 countries.
Funding
Abstract
Drug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer. Phosphoproteomic analyses identified ERK1/2 as a major output of FGF2 signaling via FGF receptors (FGFRs), with consequent up-regulation of Cyclin D1 and down-regulation of Bim as mediators of drug resistance. FGF2-driven drug resistance in anti-estrogen-sensitive and -resistant models, including patient-derived xenografts, was reverted by neutralizing FGF2 or FGFRs. A transcriptomic signature of FGF2 signaling in primary tumors predicted shorter recurrence-free survival independently of age, grade, stage, and FGFR amplification status. These findings delineate FGF2 signaling as a ligand-based drug resistance mechanism and highlights an underdeveloped aspect of precision oncology: characterizing and treating patients according to their TME constitution.
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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.