TY - JOUR AB - Angiogenesis is a process of neovascular formation from pre-existing blood vessels, which consists of sequential steps for vascular destabilization, angiogenic sprouting, lumen formation and vascular stabilization. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiopoietin, Notch, transforming growth factor-β (TGF-β), Hedgehog and WNT signaling cascades orchestrate angiogenesis through the direct or indirect regulation of quiescence, migration and the proliferation of endothelial cells. Small‑molecule compounds and human/humanized monoclonal antibodies interrupting VEGF signaling have been developed as anti‑angiogenic therapeutics for cancer and neovascular age-related macular degeneration (AMD). Gene or protein therapy delivering VEGF, FGF2 or FGF4, as well as cell therapy using endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been developed as pro‑angiogenic therapeutics for ischemic heart disease and peripheral vascular disease. Anti‑angiogenic therapy for cancer and neovascular AMD is more successful than pro‑angiogenic therapy for cardiovascular diseases, as VEGF‑signal interruption is technically feasible compared with vascular re‑construction. Common and rare genetic variants are detected using array-based technology and personal genome sequencing, respectively. Drug and dosage should be determined based on personal genotypes of VEGF and other genes involved in angiogenesis. As epigenetic alterations give rise to human diseases, polymer‑based hydrogel film may be utilized for the delivery of drugs targeting epigenetic processes and angiogenesis as treatment modalities for cardiovascular diseases. Circulating microRNAs (miRNAs) in exosomes and microvesicles are applied as functional biomarkers for diagnostics and prognostics, while synthetic miRNAs in polymer‑based nanoparticles are applicable for therapeutics. A more profound understanding of the spatio-temporal interactions of regulatory signaling cascades and advances in personal genotyping and miRNA profiling are required for the optimization of targeted therapy. AD - Division of Integrative Omics and Bioinformatics, National Cancer Center, Tokyo 104-0045, Japan AU - Katoh,Masaru DA - 2013/10/01 DO - 10.3892/ijmm.2013.1444 EP - 767 IS - 4 JO - Int J Mol Med KW - bevacizumab sunitinib sorafenib dovitinib ponatinib AZD4547 breast cancer lung cancer colorectal cancer gastric cancer field cancerization poly(lactic-co-glycolic acid) chitosan vascular medicine PY - 2013 SN - 1107-3756 1791-244X SP - 763 ST - Therapeutics targeting angiogenesis: Genetics and epigenetics, extracellular miRNAs and signaling networks (Review) T2 - International Journal of Molecular Medicine TI - Therapeutics targeting angiogenesis: Genetics and epigenetics, extracellular miRNAs and signaling networks (Review) UR - https://doi.org/10.3892/ijmm.2013.1444 VL - 32 ER -