ArticleScientific reports2019
A Selective FGFR inhibitor AZD4547 suppresses RANKL/M-CSF/OPG-dependent ostoclastogenesis and breast cancer growth in the metastatic bone microenvironment.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- Effect of colony‑stimulating factor in the mechanism of bone metastasis development (Review).Oncology reports · 2024Review
- Association of TNFRSF19 with a TNF family-based prognostic model and subtypes in gliomas using machine learning.Heliyon · 2024Article
- Receptor tyrosine kinases in breast cancer treatment: unraveling the potential.American journal of cancer research · 2024Review
- Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.Scientific reports · 2023Article
- The importance of cancer-associated fibroblasts in targeted therapies and drug resistance in breast cancer.Frontiers in oncology · 2023Review
- Review of potential medical treatments for middle ear cholesteatoma.Cell communication and signaling : CCS · 2022Review
- Cancer-associated fibroblasts in breast cancer: Challenges and opportunities.Cancer communications (London, England) · 2022Review
- AZD4547 targets the FGFR/Akt/SOX2 axis to overcome paclitaxel resistance in head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Amino-oxetanes as amide isosteres by an alternative defluorosulfonylative coupling of sulfonyl fluorides.Nature chemistry · 2022Article
- Review
- Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-κB/bone remodeling factors signaling.Molecular cancer · 2021Article
- Review
- The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives.Cancers · 2020Review
- TNFRSF11B activates Wnt/β-catenin signaling and promotes gastric cancer progression.International journal of biological sciences · 2020Article
- CaSR Induces Osteoclast Differentiation and Promotes Bone Metastasis in Lung Adenocarcinoma.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of fibroblast growth factor receptor (FGFR) signalling contributes to progression and metastasis of many types of cancers including breast cancer. Accordingly, FGFR targeted tyrosine kinase inhibitors (TKIs) are currently under development. However, the efficacy of FGFR TKIs in the bone microenvironment where breast cancer cells most frequently metastasize and also where FGFR is biologically active, has not been clearly investigated. We investigated the FGFR-mediated interactions among cancer and the bone microenvironment stromal cells (osteoblasts and osteoclasts), and also the effects of FGFR inhibition in bone metastasis. We showed that addition of culture supernatant from the MDA-MB-134-VI FGFR-amplified breast cancer cells-activated FGFR siganalling in osteoblasts, including increased expression of RANKL, M-CSF, and osteoprotegerin (OPG). Further in vitro analyses showed that AZD4547, an FGFR TKI currently in clinical trials for breast cancer, decreased RANKL and M-CSF, and subsequently RANKL and M-CSF-dependent osteoclastogenesis of murine bone marrow monocytes. Moreover, AZD4547 suppressed osteoclastogenesis and tumor-induced osteolysis in an orthotopic breast cancer bone metastasis mouse model using FGFR non-amplified MDA-MB-231 cells. Collectively, our results support that FGFR inhibitors inhibit the bone microenvironment stromal cells including osteoblasts and osteoclasts, and effectively suppress both tumor and stromal compartments of bone metastasis.
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