ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Pooled it
- Randomized Phase 2 Trial of Presurgical Androgen Deprivation Therapy With or Without Axitinib in Prostate Cancer Presenting With Lymph Node Metastasis.European urology oncology · 2025Trial
- Immunological biomarkers of response and resistance to treatment with cabozantinib and nivolumab in recurrent endometrial cancer.Journal for immunotherapy of cancer · 2025Trial
- Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.Clinical genitourinary cancer · 2020Trial
- Longitudinally Monitoring Prostate Cancer Bone Metastasis and Treatment Response via Circulating Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- The HGF/MET Axis in Advanced Prostate Cancer: From Context-Dependent Biology to Biomarker-Driven Therapeutic Strategies.Cancers · 2026Review
- Dual role of autophagy in bone metastasis: mechanistic insights and therapeutic targeting.American journal of clinical and experimental urology · 2025Review
- Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone.Cancer research communications · 2024Article
- Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.Cancers · 2024Review
- Characterization of prostate cancer adrenal metastases: dependence upon androgen receptor signaling and steroid hormones.Prostate cancer and prostatic diseases · 2023Article
- Experimental in vitro, ex vivo and in vivo models in prostate cancer research.Nature reviews. Urology · 2023Review
- Transcriptomic Signature and Growth Factor Regulation of Castration-Tolerant Prostate Luminal Progenitor Cells.Cancers · 2022Article
- Fibroblast Growth Factor Receptor 1 Drives the Metastatic Progression of Prostate Cancer.European urology oncology · 2022Article
- 3D Ultrasound-Guided Photoacoustic Imaging to Monitor the Effects of Suboptimal Tyrosine Kinase Inhibitor Therapy in Pancreatic Tumors.Frontiers in oncology · 2022Article
- Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel.Oncogene · 2021Article
- Nanotechnology-Based Strategies to Evaluate and Counteract Cancer Metastasis and Neoangiogenesis.Advanced healthcare materials · 2021Review
- Co-dependency for MET and FGFR1 in basal triple-negative breast cancers.NPJ breast cancer · 2021Article
- Cabozantinib for HCC Treatment, From Clinical Back to Experimental Models.Frontiers in oncology · 2021Review
- Cabozantinib can block growth of neuroendocrine prostate cancer patient-derived xenografts by disrupting tumor vasculature.PloS one · 2021Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe performed parallel investigations in cabozantinib-treated patients in a phase II trial and simultaneously in patient-derived xenograft (PDX) models to better understand the roles of MET and VEGFR2 as targets for prostate cancer therapy. EXPERIMENTAL
designIn the clinical trial, radiographic imaging and serum markers were examined, as well as molecular markers in tumors from bone biopsies. In mice harboring PDX intrafemurally or subcutaneously, cabozantinib effects on tumor growth, MET, PDX in which MET was silenced, VEGFR2, bone turnover, angiogenesis, and resistance were examined.
resultsIn responsive patients and PDX, islets of viable pMET-positive tumor cells persisted, which rapidly regrew after drug withdrawal. Knockdown of MET in PDX did not affect tumor growth in mice nor did it affect cabozantinib-induced growth inhibition but did lead to induction of FGFR1. Inhibition of VEGFR2 and MET in endothelial cells reduced the vasculature, leading to necrosis. However, each islet of viable cells surrounded a VEGFR2-negative vessel. Reduction of bone turnover was observed in both cohorts.
conclusionsOur studies demonstrate that MET in tumor cells is not a persistent therapeutic target for metastatic castrate-resistant prostate cancer (CRPC), but inhibition of VEGFR2 and MET in endothelial cells and direct effects on osteoblasts are responsible for cabozantinib-induced tumor inhibition. However, vascular heterogeneity represents one source of primary therapy resistance, whereas induction of FGFR1 in tumor cells suggests a potential mechanism of acquired resistance. Thus, integrated cross-species investigations demonstrate the power of combining preclinical models with clinical trials to understand mechanisms of activity and resistance of investigational agents.
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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.