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Aptamer Therapeutics in Cancer: Current and Future
#MMPMID29562664
Morita Y
; Leslie M
; Kameyama H
; Volk DE
; Tanaka T
Cancers (Basel)
2018[Mar]; 10
(3
): ä PMID29562664
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Aptamer-related technologies represent a revolutionary advancement in the
capacity to rapidly develop new classes of targeting ligands. Structurally
distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding
molecules and exhibit high binding affinity and selectivity. Although their
molecular weight is relatively small-approximately one-tenth that of monoclonal
antibodies-their complex tertiary folded structures create sufficient recognition
surface area for tight interaction with target molecules. Additionally, unlike
antibodies, aptamers can be readily chemically synthesized and modified. In
addition, aptamers' long storage period and low immunogenicity are favorable
properties for clinical utility. Due to their flexibility of chemical
modification, aptamers are conjugated to other chemical entities including
chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for
therapeutic and diagnostic applications. However, as relatively small sized
oligonucleotides, aptamers present several challenges for successful clinical
translation. Their short plasma half-lives due to nuclease degradation and rapid
renal excretion necessitate further structural modification of aptamers for
clinical application. Since the US Food and Drug Administration (FDA) approval of
the first aptamer drug, Macugen(®) (pegaptanib), which treats wet-age-related
macular degeneration, several aptamer therapeutics for oncology have followed and
shown promise in pre-clinical models as well as clinical trials. This review
discusses the advantages and challenges of aptamers and introduces therapeutic
aptamers under investigation and in clinical trials for cancer treatments.
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