ArticleOncotarget2016
Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Trial
- Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer.Angiogenesis · 2019Trial
- RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2026Article
- Targeting multiple receptor tyrosine kinases with sitravatinib: A Phase 1b study in advanced renal cell carcinoma and castrate-resistant prostate cancer.Investigational new drugs · 2024Article
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease.International journal of molecular sciences · 2021Review
- Angiogenesis inhibitors for advanced hepatocellular carcinoma: in search for the right partner.Annals of translational medicine · 2020Article
- Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts.Oncogenesis · 2019Article
- A Phase Ib, Open-Label Study of Dalantercept, an Activin Receptor-Like Kinase 1 Ligand Trap, plus Sorafenib in Advanced Hepatocellular Carcinoma.The oncologist · 2019Article
- Bone Morphogenetic Proteins in Vascular Homeostasis and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- ALK1 signaling in development and disease: new paradigms.Cellular and molecular life sciences : CMLS · 2017Review
- Early Actions of Anti-Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Drugs on Angiogenic Blood Vessels.The American journal of pathology · 2017Article
- Kinomic profiling identifies focal adhesion kinase 1 as a therapeutic target in advanced clear cell renal cell carcinoma.Oncotarget · 2017Article
- Impact of selective anti-BMP9 treatment on tumor cells and tumor angiogenesis.Molecular oncology · 2016Article
- Activin receptor-like kinases: a diverse family playing an important role in cancer.American journal of cancer research · 2016Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Treatment of metastatic renal cell carcinoma (mRCC) with agents that block signaling through vascular endothelial growth factor receptor 2 (VEGFR2) induces disease regression or stabilization in some patients; however, these responses tend to be short-lived. Therefore, development of combination therapies that can extend the efficacy of VEGFR antagonists in mRCC remains a priority.We studied murine xenograft models of RCC that become refractory to treatment with the VEGFR tyrosine kinase inhibitor (TKI) sunitinib. Dalantercept is a novel antagonist of Activin receptor-like kinase 1 (ALK1)/Bone morphogenetic protein (BMP) 9 signaling. Dalantercept inhibited growth in the murine A498 xenograft model which correlated with hyperdilation of the tumor vasculature and an increase in tumor hypoxia. When combined with sunitinib, dalantercept induced tumor necrosis and prevented tumor regrowth and revascularization typically seen with sunitinib monotherapy in two RCC models. Combination therapy led to significant downregulation of angiogenic genes as well as downregulation of endothelial specific gene expression particularly of the Notch signaling pathway. We demonstrate that simultaneous targeting of molecules that control distinct phases of angiogenesis, such as ALK1 and VEGFR, is a valid strategy for treatment of mRCC. At the molecular level, combination therapy leads to downregulation of Notch signaling.
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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.