From proteins to nucleic acid-based drugs: the role of biotech in anti-VEGF therapy.
Cancer cells, by releasing pro-angiogenic factors, stimulate the growth of the thick capillary net necessary for the nourishment of the tumor mass. The battle to defeat cancer uses today different approaches based on the inhibition of pathological angiogenesis: several compounds, either synthetic or biotech, aimed at this complex process, are under development. Vascular endothelial growth factor (VEGF) is considered the main target for an anti-cancer therapy based on angiogenesis inhibition; the goal is to block the interaction between this cytokine and its receptors in order to stop the intracellular signaling pathways leading to endothelium remodeling. FDA recently approved two drugs specifically aimed at VEGF, bevacizumab, a humanized monoclonal antibody, and pegaptinib, a pegylated aptamer with application in ophthalmic pathologies. These two approvals validate anti-VEGF therapy for clinical use, and show how biotech companies are investing on angiogenesis using different approaches, i.e. exploiting protein drugs and oligonucleotide-based therapeutics. Monoclonal antibodies, as well as other high molecular weight products like cytokine-traps, aptamers and short interfering RNA (siRNA), are designed to target VEGF and its receptors. Their design, production and clinical advancement in cancer and other pathological conditions linked to angiogenesis will be specifically addressed in this review.
Gatto
Barbara
B
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy. barbara.gatto@unipd.it
Cavalli
Marco
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide / Q000494:pharmacology / Q000627:therapeutic use; D000068258:Bevacizumab; D018849:Controlled Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D015202:Protein Engineering; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use; D000069579:Ranibizumab; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000819:agonists*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D034741:RNA, Small Interfering; D042442:Vascular Endothelial Growth Factors; C495058:pegaptanib; D000068258:Bevacizumab; D040301:Vascular Endothelial Growth Factor Receptor-2; D000069579:Ranibizumab