ArticleJournal of endocrinological investigation2012
Anti-tumor activity of motesanib in a medullary thyroid cancer model.
Article in Journal of endocrinological investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.Gynecologic oncology · 2013Trial
- Effect of topical motesanib in experimental corneal neovascularization model.International ophthalmology · 2023Review
- ONC201 Shows Potent Anticancer Activity Against Medullary Thyroid Cancer via Transcriptional Inhibition ofMolecular cancer therapeutics · 2021Article
- Medullary Thyroid Cancer: Clinical Characteristics and New Insights into Therapeutic Strategies Targeting Tyrosine Kinases.Molecular diagnosis & therapy · 2017Review
- The molecular basis for RET tyrosine-kinase inhibitors in thyroid cancer.Best practice & research. Clinical endocrinology & metabolism · 2017Review
- The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.European journal of medicinal chemistry · 2016Article
- Biomarkers for anti-angiogenic therapy in cancer.International journal of molecular sciences · 2013Review
- Activated RET and ROS: two new driver mutations in lung adenocarcinoma.Translational lung cancer research · 2013Review
- Advanced medullary thyroid cancer: pathophysiology and management.Cancer management and research · 2013Article
- Cellular signaling pathway alterations and potential targeted therapies for medullary thyroid carcinoma.International journal of endocrinology · 2013Article
- Antitumor activity of motesanib alone and in combination with cisplatin or docetaxel in multiple human non-small-cell lung cancer xenograft models.Molecular cancer · 2012Article
- RET TKI: potential role in thyroid cancers.Current oncology reports · 2012Review
- New targeted therapies for thyroid cancer.Current genomics · 2011Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMedullary thyroid cancer (MTC) is frequently associated with mutations in the tyrosine kinase Ret and with increased expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2). Motesanib is an investigational, orally administered small molecule antagonist of VEGFR1, 2, and 3; platelet-derived growth factor receptor (PDGFR); Kit; and possibly Ret.
aimThe aim of this study was to investigate the effects of motesanib on wildtype and mutant Ret activity in vitro and on tumor xenograft growth in a mouse model of MTC. METHODS/
resultsIn cellular phosphorylation assays, motesanib inhibited the activity of wild-type Ret (IC(50)=66 nM), while it had limited activity against mutant Ret C634W (IC(50)=1100 nM) or Ret M918T (IC(50)>2500 nM). In vivo, motesanib significantly inhibited the growth of TT tumor cell xenografts (expressing Ret C634W) and significantly reduced tumor blood vessel area and tumor cell proliferation, compared with control. Treatment with motesanib resulted in substantial inhibition of Ret tyrosine phosphorylation in TT xenografts and, at comparable doses, in equivalent inhibition of VEGFR2 phosphorylation in both TT xenografts and in mouse lung tissue.
conclusionsThe results of this study demonstrate that motesanib inhibited thyroid tumor xenograft growth predominantly through inhibition of angiogenesis and possibly via a direct inhibition of VEGFR2 and Ret expressed on tumor cells. These data suggest that targeting angiogenesis pathways and specifically the VEGF pathway may represent a novel therapeutic approach in the treatment of MTC.
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