ArticleOncotarget2017
Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Phase II Study of Cabozantinib in Patients With Bone Metastasis.The oncologist · 2022Trial
- Randomized Phase II Trial and Tumor Mutational Spectrum Analysis from Cabozantinib versus Chemotherapy in Metastatic Uveal Melanoma (Alliance A091201).Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- TFE3-rearranged and TFEB-altered renal cell carcinoma: from classification to real-life. Insights from a national Italian survey.Pathologica · 2025Article
- SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway.Open life sciences · 2025Article
- Review
- Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib, Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment.International journal of molecular sciences · 2022Article
- Poor bone matrix quality: What can be done about it?Current osteoporosis reports · 2021Review
- Article
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
- Targeting the VEGF Pathway in Osteosarcoma.Cells · 2021Review
- Review
- Current and Emerging Biomarkers Predicting Bone Metastasis Development.Frontiers in oncology · 2020Review
- MiR-128 inhibits the osteogenic differentiation in osteoporosis by down-regulating SIRT6 expression.Bioscience reports · 2019Article
- Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases.International journal of molecular sciences · 2019Review
- An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma.Nature reviews. Urology · 2018Review
- Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts.Cancers · 2018Review
- Cabozantinib Affects Osteosarcoma Growth Through A Direct Effect On Tumor Cells and Modifications In Bone Microenvironment.Scientific reports · 2018Article
- Paeoniflorin regulates osteoclastogenesis and osteoblastogenesis via manipulating NF-κB signaling pathway bothOncotarget · 2018Article
- Article
- Cabozantinib in metastatic renal cell carcinoma: latest findings and clinical potential.Therapeutic advances in medical oncology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and bone resorption assays and osteoblast differentiation was detected by alkaline phosphatase and alizarin red staining.Our results show that non-cytotoxic doses of cabozantinib significantly inhibit osteoclast differentiation (p=0.0145) and bone resorption activity (p=0.0252). Moreover, cabozantinib down-modulates the expression of osteoclast marker genes, TRAP (p=0.006), CATHEPSIN K (p=0.004) and Receptor Activator of Nuclear Factor k B (RANK) (p=0.001). Cabozantinib treatment has no effect on osteoblast viability or differentiation, but increases osteoprotegerin mRNA (p=0.015) and protein levels (p=0.004) and down-modulates Receptor Activator of Nuclear Factor k B Ligand (RANKL) at both mRNA (p<0.001) and protein levels (p=0.043). Direct cell-to-cell contact between cabozantinib pre-treated osteoblasts and untreated osteoclasts confirmed the indirect anti-resorptive effect of cabozantinib.We demonstrate that cabozantinib inhibits osteoclast functions "directly" and "indirectly" reducing the RANKL/osteoprotegerin ratio in osteoblasts.
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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.