Clinical implications of circulating angiogenic factors in cancer patients

Purpose: Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. Methods: A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. Results: A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGE may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. Conclusion: Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.