Angiogenic factors as potential drug target: Efficacy and limitations of anti-angiogenic therapy |
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| Authors: | Rajesh N. Gacche Rohan J. Meshram |
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| Affiliation: | School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded-431 606 (MS), India |
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| Abstract: | Formation of new blood vessels (angiogenesis) has been demonstrated to be a basic prerequisite for sustainable growth and proliferation of tumor. Several growth factors, cytokines, small peptides and enzymes support tumor growth either independently or in synergy. Decoding the crucial mechanisms of angiogenesis in physiological and pathological state has remained a subject of intense interest during the past three decades. Currently, the most widely preferred approach for arresting tumor angiogenesis is the blockade of vascular endothelial growth factor (VEGF) pathway; however, the clinical usage of this modality is still limited by several factors such as adverse effects, toxicity, acquired drug resistance, and non-availability of valid biomarkers. Nevertheless, angiogenesis, being a normal physiological process imposes limitations in maneuvering it as therapeutic target for tumor angiogenesis. The present review offers an updated relevant literature describing the role of well-characterized angiogenic factors, such as VEGF, basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), placenta growth factor (PLGF), hepatocyte growth factor/scatter factor (HGF/SF) and angiopoetins (ANGs) in regulating tumor angiogenesis. We have also attempted to discuss tumor angiogenesis with a perspective of ‘an attractive target with emerging challenges’, along with the limitations and present status of anti-angiogenic therapy in the current state-of-the-art. |
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| Keywords: | VEGF, vascular endothelial growth factor CRC, colorectal cancer VEGFR, VEGF receptors PLGF, placental growth factor HGF, hepatocyte growth factor Il, Interleukin Del-1, developmentally-regulated endothelial cell locus 1 protein FGF, fibroblast growth factors CXCL1/Groα, growth-regulated alpha protein CXCL6/GCP2, granulocyte chemotactic protein 2 bFGF, basic fibroblast growth factor PDGF, platelet derived growth factor HGF/SF, hepatocyte growth factor/scatter factor ANG, angiopoetin VPF, vascular permeability factor kDa, kilo Dalton Flt, Fms-like tyrosine kinase Flk, fetal liver kinase KDR, kinase insert domain receptor HIF-1α, hypoxia inducible factors NRP, neuropilin SAF-1, serum amyloid A activating factor 1 HPSGs, heparan sulfate proteoglycans FGFR, fibroblast growth factor receptors PDGF-B, platelet-derived growth factor-Beta miR, microRNA FP1039, Five Prime Therapeutics EC, endothelial cell MMP, matrix metalloproteases ET-1, endothelin-1 TGF, transforming growth factor TNF, tumor necrosis factor PO2, partial pressure of oxygen SMCs, smooth muscle cells HUVEC, human umbilical vein endothelial cell MAPK, Mitogen-activated protein kinase PI3K, Phosphoinositide 3-kinase PKC-zeta, Protein kinase C zeta Sp1, specificity protein 1 U1snRNA, U1 small nuclear RNA Tie-2, tunica intima endothelial kinase 2 GBM, glioblastoma multiforme Erk, extracellular signal-regulated kinase TKIs, tyrosine kinase inhibitors mTOR, mammalian target of rapamycin EGFR, epidermal growth factor receptor Dll4, delta-like ligand 4 ECP, endothelial cell progenitor G-CSF, granulocyte colony-stimulating factor SDF, stromal derived factor CECs, circulating endothelial cells VCAMs, vascular cell adhesion proteins NPDD, nanoparticle mediated drug delivery hCG, human chorionic gonadotropin ESDN, endothelial and smooth muscle cell-derived neuropilin-like protein |
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