Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic

• Published in: Frontiers in chemistry Vol. 2; p. 87
• Main Authors: Moreno, Pedro M D, Pêgo, Ana P
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01-01-2014
• Subjects: antisense; Cancer; Chemistry; Nanomedicine; Oligonucleotides; Therapeutics; nanomedicine; therapeutics; cancer; oligonucleotides; antisense
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2014.00087

Under clinical development since the early 90's and with two successfully approved drugs (Fomivirsen and Mipomersen), oligonucleotide-based therapeutics has not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given toward a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.