The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion

Malignant pleural effusions (MPEs) are a significant source of cancer-related morbidity. Over 150,000 patients in the United States suffer from breathlessness and diminished quality of life due to MPE each year. Current management strategies are of mostly palliative value and focus on symptom control; they do not address the pathobiology of the effusion, nor do they improve survival. Further elucidation of the pathophysiological mechanisms, coupled with the development of novel treatments such as intrapleural chemotherapeutics targeting this process, has the potential to greatly improve the efficacy of our current management options. Vascular endothelial growth factor-A (VEGF-A) has been implicated as a critical cytokine in the formation of malignant pleural effusions. Elevated levels of VEGF produced by tumor cells, mesothelial cells, and infiltrating immune cells result in increased vascular permeability, cancer cell transmigration, and angiogenesis. Therefore antiangiogenic therapies such as Bevacizumab, a monoclonal antibody targeting VEGF-A, may have a potential role in the management of malignant pleural effusions. Herein we review the pathogenesis and potential treatment strategies of malignant pleural effusions, with a focus on angiogenesis and antiangiogenic therapeutics.