The role of angiopoietins as potential therapeutic targets in renal cell carcinoma
| Autor: | Michael B. Atkins, David C. Alsop, Xiaoen Wang, Dongyin Yu, Andrea J. Bullock, James W. Mier, Rupal S. Bhatt, Kedar Mahagaokar, Liang Zhang, Angela Coxon, Lin Wei, Jon Oliner |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Cancer Research Angiogenesis urologic and male genital diseases Article Neovascularization Downregulation and upregulation Renal cell carcinoma Internal medicine medicine chemistry.chemical_classification business.industry Sunitinib Cancer Angiopoietins medicine.disease female genital diseases and pregnancy complications 3. Good health Endocrinology chemistry Oncology Cancer research medicine.symptom business Glycoprotein medicine.drug |
| Zdroj: | Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors. |
| Databáze: | OpenAIRE |
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