Angiogenic factors as potential drug target: Efficacy and limitations of anti-angiogenic therapy

• Published in: Biochimica et biophysica acta Vol. 1846; no. 1; pp. 161 - 179
• Main Authors: Gacche, Rajesh N., Meshram, Rohan J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2014
• Subjects: Angiogenesis Inhibitors - therapeutic use; Angiogenic Proteins - antagonists & inhibitors; Animals; Anti-angiogenic therapy; Cell Proliferation - drug effects; Genes, Switch; Humans; Molecular Targeted Therapy; Neoplasms - blood supply; Neoplasms - drug therapy; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Pro-angiogenic cytokines; Treatment Outcome; Tumor angiogenesis; PKC-zeta; HIF-1α; HPSGs; NRP; TNF; PO2; PI3K; SDF; VEGFR; KDR; mTOR; ESDN; EC; VCAMs; Del-1; FGF; HGF; TKIs; Tumor angiogenesis; PDGF-B; MAPK; G-CSF; bFGF; MMP; TGF; ET-1; CRC; miR; ANG; Erk; Il; Flk; Tie-2; kDa; SMCs; VPF; hCG; EGFR; Flt; Dll4; GBM; Sp1; U1snRNA; HUVEC; HGF/SF; VEGF; NPDD; Pro-angiogenic cytokines; SAF-1; FGFR; CECs; CXCL6/GCP2; Anti-angiogenic therapy; ECP; CXCL1/Groα; PDGF; PLGF; FP1039
• ISSN: 0304-419X; 0006-3002; 1879-2561
• DOI: 10.1016/j.bbcan.2014.05.002

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. [Display omitted] •Role of major angiogenic factors supporting tumor growth•Angiogenesis as an attractive target: Limitations and challenges•Decoding angiogenic switch for regulation of angiogenesis•Current status of anti-angiogenic therapy•Factors limiting the efficacy of anti-angiogenic therapy•Future prospectus of the anti-angiogenic therapy