Targeting tumor micro-environment for design and development of novel anti-angiogenic agents arresting tumor growth

• Published in: Progress in biophysics and molecular biology Vol. 113; no. 2; pp. 333 - 354
• Main Authors: Gacche, Rajesh N., Meshram, Rohan J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2013
• Subjects: Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Angiogenic cytokines/peptides; angiogenic proteins; Angiogenic Proteins - metabolism; Animals; Antiangiogenic agents; antineoplastic agents; blood vessels; Cell Proliferation - drug effects; clinical trials; cytokines; endothelial cells; epidermal growth factor; fibroblast growth factors; Humans; hypoxia; metastasis; Models, Biological; Molecular Targeted Therapy - methods; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; nerve growth factor; placenta; receptors; transforming growth factors; Tumor Microenvironment - drug effects; Tumor Microenvironment - physiology; vascular endothelial growth factors; Nrp1; PHDs; IL1R; CLR; Angiogenesis; p55; Tie2K; PGDF; CDRs; EC; Nrp 2; CML; FGF; IL-1; PGFR; HGF; Angiogenic cytokines/peptides; IR; SDF-1alpha; IL-3; NGF; AM; PGF; IL-6; PGDFR; Angp-2; Angp-1; RAMP; MIP; GPCR; Ang; CGRP; IL-6r; CXCR4; NTS; RNase-A; PDB; p75; HIF-1; VHD; CXCR1; TGF-α; Antiangiogenic agents; CXCR2; SDF-1α; TGF-β; DHLA; AMBP-1; IGF-1R; JAKs; TNFR; FIH; EGF; VEGF; epidermal growth factor receptor; IGFBPs; IGF; VEGF Receptor; PAMP; TNF-α; ALA; SCF; MCP; ATP; IGF-2R; interleukin-3; interleukin-1; transforming growth factor-beta; Tumor necrosis factor-alpha; Neuropilin2; calcitonin receptor-like receptor; placenta growth factor receptor; Neuropilin1; complementarity-determining regions; placenta growth factor; VEGF homology domain; CXC receptor4; CXC receptor2; CXC receptor1; TNF-receptor; interleukin 6 receptor; epidermal growth factor; endothelial cells; transforming growth factor-alpha; type I IL-1 receptor; nerve growth factor; protein data bank; alpha linolenic acid; angiopoietin-2; 75 kDa protein; platelet derived growth factor receptor; IGF-binding proteins; calcitonin gene-related peptide; angiogenin; adenosine triphosphate; macrophage inflammatory protein; 55 kDa protein; hypoxia inducible factor-1; insulin-like growth factor receptor type2; insulin-like growth factor receptor type1; Angiopoietin-1; interleukin 6; fibroblast growth factor; stromal cell-derived factor-1α; VEGFR; insulin-like growth factor; cytoplasmic kinase domain of Tie2; chronic myelogenous leukemia; G protein coupled receptors; dihomo gamma-linolenic acid; AM binding protein-1; platelet derived growth factor; prolyl hydroxylases; proadrenomedullin N-terminal 20 peptide; Factor-inhibiting hypoxia-inducible factor; ribonuclease-A; EGFR; stem-cell factor; receptor activity modifying protein; hepatocyte growth factor; monocyte chemotactic protein; janus kinases; insulin receptors; andrenomedullin; vascular endothelial growth factor; 1,3,6-Naphthalenetrisulfonate
• ISSN: 0079-6107; 1873-1732; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2013.10.001

Angiogenesis: a process of generation of new blood vessels has been proved to be necessary for sustained tumor growth and cancer progression. Inhibiting angiogenesis pathway has long been remained a significant hope for the development of novel, effective and target orientated antitumor agents arresting the tumor proliferation and metastasis. The process of neoangiogenesis as a biological process is regulated by several pro- and anti-angiogenic factors, especially vascular endothelial growth factor, fibroblast growth factor, epidermal growth factor, hypoxia inducible factor 1 and transforming growth factor. Every endothelial cell destined for vessel formation is equipped with receptors for these angiogenic peptides. Moreover, numerous other angiogenic cytokines such as platelet derived growth factor (PGDF), placenta growth factor (PGF), nerve growth factor (NGF), stem-cell factor (SCF), and interleukins-2, 4, 6 etc. These molecular players performs critical role in regulating the angiogenic switch. Couple of decade's research in molecular aspects of tumor biology has unraveled numerous structural and functional mysteries of these angiogenic peptides. In present article, a detailed update on the functional and structural peculiarities of the various angiogenic peptides is described focusing on structural opportunities made available that has potential to be used to modulate function of these angiogenic peptides in developing therapeutic agents targeting neoplastic angiogenesis. The data may be useful in the mainstream of developing novel anticancer agents targeting tumor angiogenesis. We also discuss major therapeutic agents that are currently used in angiogenesis associated therapies as well as those are subject of active research or are in clinical trials.