[Frontiers in Bioscience 16, 740-748, January 1, 2011]

Antiangiogenic therapies for malignant pleural mesothelioma

Seiji Yano1, Qi Li1, Wei Wang1, Tadaaki Yamada1, Shinji Takeuchi1, Emiko Nakataki2, Hirokazu Ogino2, Hisatsugu Goto2, Yasuhiko Nishioka2, Saburo Sone2

1Division of Medical Oncology, Cancer Research Institute, Kanazawa University. Kanazawa, Ishikawa 920-0934, 2Department of Respiratory Medicine and Rheumatology, University of Tokushima Graduate School, Tokushima, Tokushima 770-8503, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction (Clinical features of malignant pleural mesothelioma)
3. Malignant pleural mesothelioma and angiogenesis
4. Establishment of orthotopic implantation models for malignant pleural mesothelioma
5. Correlation between progression pattern and proangiogenic cytokine production in the orthotopic models
6. Therapeutic strategy for high-VEGF-producing malignant pleural mesothelioma
6.1. Anti-VEGF antibody, bevacizumab
6.2. Triple tyrosine kinase inhibitor, vandetanib
7. Therapeutic strategy for low-VEGF--producing malignant pleural mesothelioma
8. Future assignments
9. Acknowledgements
10. References

1. ABSTRACT

Malignant pleural mesothelioma (MPM), arises from the mesothelial cells, is difficult to be diagnosed at an early stage, and is refractory to conventional chemotherapy and radiotherapy. Therefore, the establishment of novel effective therapies is necessary to improve the prognosis for many patients with this disease. Recent studies have demonstrated that angiogenesis plays a significant role in MPM progression, suggesting the importance of tumor vessels as therapeutic targets. To explore molecular pathogenesis and evaluate the efficacy of vascular targeting therapy in MPM, we developed orthotopic implantation SCID mouse models of MPM. We found that selective VEGF inhibitors were effective only in the treatment of high-VEGF-producing MPM models. On the other hand, multiple kinase inhibitor E7080, with inhibitory activity against various angiogenic cytokine receptors, suppressed the progression and prolonged survival of both high-VEGF-producing and low-VEGF-producing MPM models. Further understanding of the functional characteristics of tumor angiogenesis may be essential to improve targeting therapies in MPM. In this review, we introduce current status of clinical strategies and novel therapeutic approaches against angiogenesis in MPM.