title: Opportunities and challenges in tumor angiogenesis research: back and forth between bench and bed.
abstract: Angiogenesis is essential for tumor growth and metastasis. Many signaling pathways are involved in regulating tumor angiogenesis, with the vascular endothelial growth factor pathway being of particular interest. The recognition of the heterogeneity in tumor vasculature has led to better predictions of prognosis through differential analyses of the vasculature. However, the clinical benefits from antiangiogenic therapy are limited, because many antiangiogenic agents cannot provide long-term survival benefits, suggesting the development of drug resistance. Activation of the hypoxia and c-Met pathways, as well as other proangiogenic factors, has been shown to be responsible for such resistance. Vessel co-option could be another important mechanism. For future development, research to improve the efficacy of antiangiogenic therapy includes (a) using tumor-derived endothelial cells for drug screening; (b) developing the drugs focusing on specific tumor types; (c) developing a better preclinical model for drug study; (d) developing more accurate biomarkers for patient selection; (e) targeting the c-Met pathway or other pathways; and (f) optimizing the dose and schedule of antiangiogenic therapy. In summary, the future of antiangiogenic therapy for cancer patients depends on our efforts to develop the right drugs, select the right patients, and optimize the treatment conditions.
authors.affiliation: State Key Laboratory on Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bromberg-White
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D049109:Cell Proliferation; D006801:Humans; D000860:Hypoxia / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D055806:Microvessels / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042442:Vascular Endothelial Growth Factors; C546842:MTOR protein, human; D019859:Proto-Oncogene Proteins c-met; D058570:TOR Serine-Threonine Kinases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic