title: Potential role of soluble VEGFR-1 in antiangiogenesis therapy for cancer.
abstract: Antiangiogenesis therapy for cancer may inhibit tumor growth and metastasis when combined with chemotherapy, and has received a great deal of attention over recent years. However, accurate assessments of biological efficacy and toxicity are major hurdles for this approach. Soluble VEGF receptor-1 (sFlt-1) has been reported to have a role in the pathogenesis of preeclampsia, the hallmark of which is similar to the toxicities related to antiangiogenesis therapy. Clinical evidence and animal studies support the hypothesis that sFlt-1 may contribute to hypertension and proteinuria in patients treated with anti-VEGF agents. The intratumoral imbalance between sFlt-1 and VEGF levels correlates with the malignancy grades of tumors, survival and responsiveness to therapy. The therapeutic potential of sFlt-1 as an antiangiogenic agent has been validated by an increasing number of preclinical studies. Furthermore, antiangiogenesis therapy changes the concentration of circulating VEGF, PlGF, sFlt-1, soluble VEGFR-2 and even soluble VEGFR-3, with some of these being identified as potential biomarkers of response and toxicity. All these factors suggest that sFlt-1 may prove invaluable for driving the future development of molecular therapeutics with novel targets and mechanisms of action, and its impact on antiangiogenesis therapy in cancers needs further investigation.
authors.affiliation: Pancreatic Disease Institute, Department of Pancreatic Surgery, Huashan Hospital, 12 Central Urumqi Road, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.forename: Yong-jian
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Di
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Fu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1