Recent findings in mesothelioma cell biology
Angiogenesis Weekly
August 1, 2008
Data detailed in 'Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement' have been presented. "Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a poor prognosis, therefore development of novel effective therapies is urgent. In the present study, we investigated the therapeutic efficacy of vandetanib (ZD6474), an inhibitor of VEGFR-2, EGFR and RET tyrosine kinases, in an orthotopic model of MPM," researchers in Tokushima, Japan report (see also Mesothelioma Cell Biology).
"We found that a human MPM cell line, EHMES-10, expressed RET/PTC3 oncogenic rearrangement and a large amount of VEGF. Vandetanib induced the apoptosis and inhibited the proliferation of EHMES-10 cells in vitro (IC(50)=0.3 microM). Once-daily oral treatment with vandetanib inhibited tumor angiogenesis, and reduced significantly the growth of thoracic tumors and the production of pleural effusions, resulting in the prolonged survival of mice in EHMES-10 orthograft model. In contrast, the selective EGFR tyrosine kinase inhibitor, gefitinib, had no effect against EHMES-10 cells both in vitro and in vivo," wrote H. Ogino and colleagues, University of Tokushima, Institute of Health Bioscience.
The researchers concluded: "Our results suggest that using vandetanib to target RET-dependent tumor cell proliferation and survival and VEGFR-2-dependent tumor angiogenesis may be promising against MPM expressing RET oncogenic rearrangement and VEGF."
Ogino and colleagues published their study in Cancer Letters (Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement. Cancer Letters, 2008;265(1):55-66).
For additional information, contact H. Ogino, University of Tokushima Graduate School, Dept. of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Publisher contact information for the journal Cancer Letters is: Elsevier Science Ireland Ltd., Customer Relations Manager, Bay 15, Shannon Industrial Estate, Co. Clare, Ireland.
Keywords: Japan, Tokushima, Mesothelioma Cell Biology, Angiogenesis, Apoptosis, Cancer, Cell Biology, Mesothelioma, Oncology, Proteins, Proteomics, Therapy, Treatment, Tumor Vascularization, Tyrosine Kinase, Vascular Endothelial Growth Factor.
