The Use of Tyrosine Kinase Inhibitors in Modifying the Response of Tumor Microvasculature to Radiotherapy
| Autor: | Eric Edwards, Bo Lu, Ling Geng, Jiahuai Tan, Dennis E. Hallahan, Eric T. Shinohara |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Radiation-Sensitizing Agents
Cancer Research medicine.medical_specialty medicine.medical_treatment Angiogenesis Inhibitors Fibroblast growth factor Receptor tyrosine kinase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neoplasms Internal medicine medicine Humans PI3K/AKT/mTOR pathway Neovascularization Pathologic biology Akt/PKB signaling pathway Growth factor Receptor Protein-Tyrosine Kinases Vascular endothelial growth factor Endocrinology Oncology chemistry 030220 oncology & carcinogenesis Cancer research biology.protein Tyrosine kinase Platelet-derived growth factor receptor |
| Zdroj: | Technology in Cancer Research & Treatment. 4:691-698 |
| ISSN: | 1533-0338 1533-0346 |
| DOI: | 10.1177/153303460500400614 |
| Popis: | The response of the tumor microvasculature to ionizing radiation can be modified to improve tumor control in preclinical mouse models of cancer. Recent studies have shown that a variety of cancer drugs can improve the response of cancers to radiotherapy. Protein tyrosine kinase inhibitors (TKIs) have been shown to enhance radiation-induced destruction of tumor blood vessels. Among these compounds are inhibitors of a broad spectrum of receptor tyrosine kinases (RTKs). Inhibition of RTKs attenuates downstream signaling from various angiogenic growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). RTK inhibitors with various specificities against the receptors for VEGF, PDGF, and FGF manifest significant antiangiogenic activities as well. We have shown using tumor vascular window model and tumor growth delay assays that these compounds can enhance tumor radiation response by attacking tumor microvasculature. Furthermore, we have shown that radiation and RTK inhibitors exert their antiangiogenic effect through inhibition of the PI3K/Akt signaling pathway, which results in induction of apoptosis. Our studies have provided a basis for future clinical investigations of combining radiotherapy and RTK inhibitors. |
| Databáze: | OpenAIRE |
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