title: Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives.
abstract: Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004. Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment, recent studies have shown that antiangiogenic therapy has transient and insufficient efficacy, resulting in tumor recurrence in patients after several months of treatment. Blockage of blood and oxygen supplies creates a hypoxic and acidic microenvironment in the tumor tissues, which fosters tumor cells to become more aggressive and metastatic. In 2001, Jain proposed tumor vascular normalization as an alternative approach to treating cancers based on the pioneering work on tumor blood vessels by several other researchers. At present, normalizing the disorganized tumor vasculature, rather than disrupting or blocking them, has emerged as a new option for anticancer therapy. Preclinical and clinical data have shown that tumor vascular normalization using monoclonal antibodies, proteins, peptides, small molecules, and pericytes resulted in decreased tumor size and reduced metastasis. However, current tumor vascular normalizing drugs display moderate anticancer efficacy. Accumulated data have shown that a variety of vasculogenic/angiogenic tumor cells and genes play important roles in tumor neovascularization, growth, and metastasis. Therefore, multiple-targeting of vasculogenic tumor cells and genes may improve the efficacy of tumor vascular normalization. To this end, the combination of antiangiogenic drugs with tumor vascular normalizing therapeutics, as well as the integration of Western medicine with traditional Chinese medicine, may provide a good opportunity for discovering novel tumor vascular normalizing drugs for an effective anticancer therapy.
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou 215123, China.
authors.forename: Bingxue
authors.initials: B
authors.lastname: Shang
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Cao
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015820:Cadherins / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008264:Macrophages / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D015820:Cadherins; D004365:Drugs, Chinese Herbal; D042461:Vascular Endothelial Growth Factor A; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D040262:Receptors, Vascular Endothelial Growth Factor