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Antisense therapeutics in oncology: current status

Authors Farooqi A, Rehman Z, Muntane J

Received 17 July 2014

Accepted for publication 12 September 2014

Published 3 November 2014 Volume 2014:7 Pages 2035—2042

DOI https://doi.org/10.2147/OTT.S49652

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati


Ammad Ahmad Farooqi,1 Zia ur Rehman,2 Jordi Muntane3,4

1Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan; 2Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, Pakistan; 3Department of General Surgery, Institute of Biomedicine of Seville (IBiS), Hospital Universitary "Virgen del Rocío"/CSIC/University of Seville, Sevilla, Spain; 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD o Ciberehd), Instituto de Salud Carlos III, Spain

Abstract: There is increasing progress in translational oncology and tremendous breakthroughs have been made as evidenced by preclinical and clinical trials. Data obtained from high-throughput technologies are deepening our understanding about the molecular and gene network in cancer cells and rapidly emerging in vitro and in vivo evidence is highlighting the role of antisense agents as specific inhibitors of the expression of target genes, thus modulating the response of cancer cells to different therapeutic strategies. Much information is continuously being added into various facets of molecular oncology and it is now understood that overexpression of antiapoptotic proteins, oncogenes, oncogenic microRNAs (miRNA), and fusion proteins make cancer cells difficult to target. Delivery of antisense oligonucleotides has remained a challenge and technological developments have helped in overcoming hurdles by improving the ability to penetrate cells, effective and targeted binding to gene sequences, and downregulation of target gene function. Different delivery systems, including stable nucleic acid lipid particles, have shown potential in enhancing the delivery of cargo to the target site. In this review, we attempt to summarize the current progress in the development of antisense therapeutics and their potential in medical research. We partition this multicomponent review into introductory aspects about recent breakthroughs in antisense therapeutics. We also discuss how antisense therapeutics have shown potential in resensitizing resistant cancer cells to apoptosis by targeted inhibition of antiapoptotic proteins, oncogenic miRNAs, and BCR-ABL.

Keywords: antisense oligonucleotide, siRNA, miRNA, liposomes, DNAzymes, antisense therapy

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