Aptamers: A promising chemical antibody for cancer therapy

Zhou, Gang; Wilson, George S.; Hebbard, Lionel; Duan, Wei; Liddle, Christopher; George, Jacob; Qiao, Liang

doi:10.18632/oncotarget.7178

Cited by 89 publications

(77 citation statements)

References 128 publications

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“…Therefore, the role of Fgf2 in CAF pro‐tumourigenic activity was investigated using an anti‐ Fgf2 aptamer. Aptamers are short single‐stranded DNA or RNA molecules that are selected from random sequence libraries based on their highly specific and sensitive affinity to a target molecule . We co‐cultured CAFs with tumour cell‐enriched or WT lung epithelium in the 3D colony‐forming assay.…”

Section: Resultsmentioning

confidence: 99%

Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts

Hegab

Ozaki

Kameyama

et al. 2019

The Journal of Pathology

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Cancer‐associated fibroblasts (CAFs) are known to promote tumourigenesis through various mechanisms. Fibroblast growth factor (FGF)/FGF receptor (FGFR)‐dependent lung cancers have been described. We have developed a mouse model of lung adenocarcinoma that was constructed through the induction of Fgf9 overexpression in type 2 alveolar cells. The expression of Fgf9 in adult lungs resulted in the rapid development of multiple adenocarcinoma‐like tumour nodules. Here, we have characterised the contribution of CAFs and the Fgf/Fgfr signalling pathway in maintaining the lung tumours initiated by Fgf9 overexpression. We found that CAF‐secreted Fgf2 contributes to tumour cell growth. CAFs overexpressed Tgfb, Mmp7, Fgf9, and Fgf2; synthesised more collagen, and secreted inflammatory cell‐recruiting cytokines. CAFs also enhanced the conversion of tumour‐associated macrophages (TAMs) to the tumour‐supportive M2 phenotype but did not influence angiogenesis. In vivo inhibition of Fgfrs during early lung tumour development resulted in significantly smaller and fewer tumour nodules, whereas inhibition in established lung tumours caused a significant reduction in tumour size and number. Fgfr inhibition also influenced tumour stromal cells, as it significantly abolished TAM recruitment and reduced tumour vascularity. However, the withdrawal of the inhibitor caused a significant recurrence/regrowth of Fgf/Fgfr‐independent lung tumours. These recurrent tumours did not possess a higher proliferative or propagative potential. Our results provide evidence that fibroblasts associated with the Fgf9‐induced lung adenocarcinoma provide multiple means of support to the tumour. Although the Fgfr blocker significantly suppressed the tumour and its stromal cells, it was not sufficient to completely eliminate the tumour, probably due to the emergence of alternative (resistance/maintenance) mechanism(s). This model represents an excellent tool to further study the complex interactions between CAFs, their related chemokines, and the progression of lung adenocarcinoma; it also provides further evidence to support the need for a combinatorial strategy to treat lung cancer. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Resultsmentioning

confidence: 99%

Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts

Hegab

Ozaki

Kameyama

et al. 2019

The Journal of Pathology

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“…A handful of aptamers have been developed to function as therapeutic agonists in cancer. For example, DNA aptamers targeting nucleolin, PDGF, and HER2 and RNA aptamers targeting VEGF, HER3, and EGFR have been explored . In myeloma, two aptamers have been developed as antagonists to inhibit the interaction between protein with its ligand.…”

Section: Discussionmentioning

confidence: 99%

“…Aptamers are single-stranded oligonucleotides that are isolated from RNA or ssDNA libraries via systematic evolution of ligands by exponential enrichment (SELEX). 16 Similar to antibodies, aptamers bind to their targets with high affinity and selectivity due to their unique three-dimensional structures. However, aptamers are advantageous over antibodies due to their low potential for immunogenicity, efficient tissue penetration, relatively simple synthesis, etc.…”

Section: Most Of MM Development Depends On the Interactions Between Mmentioning

confidence: 99%

“…However, inherent limitations of these antibodies/inhibitors, such as cellular cytotoxicity or off‐target effects, limit their clinical use and prompted the development of a new class of therapeutic antagonists, namely, aptamers. Aptamers are single‐stranded oligonucleotides that are isolated from RNA or ssDNA libraries via systematic evolution of ligands by exponential enrichment (SELEX) . Similar to antibodies, aptamers bind to their targets with high affinity and selectivity due to their unique three‐dimensional structures.…”

Section: Introductionmentioning

confidence: 99%

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Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Zhang

Gao

Zhou

et al. 2018

J Cellular Molecular Medi

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Hepatocyte growth factor (HGF)/c‐met pathway activation has been implicated in the pathogenesis of multiple myeloma (MM), and blocking this pathway has been considered a rational therapeutic strategy for treating MM. Aptamers are single‐stranded nucleic acid molecules that fold into complex 3D structures and bind to a variety of targets. Recently, it was reported that DNA aptamer SL1 exhibited high specificity and affinity for c‐met and inhibited HGF/c‐met signaling in SNU‐5 cells. However, as the first c‐met‐targeted DNA aptamer to be identified, application of SL1 to myeloma treatment requires further investigation. Here, we explore the potential application of SL1 in MM. Our results indicated that c‐met expression is gradually increased in MM patients and contributes to poor outcomes. SL1 selectively bound to c‐met‐positive MM cells but not to normal B cells and suppressed the growth, migration and adhesion of MM cells in vitro in a co‐culture model performed with HS5 cells, wherein SL1 inhibited HGF‐induced activation of c‐met signaling. In vivo and ex vivo fluorescence imaging showed that SL1 accumulated in the c‐met positive tumour areas. In addition, SL1 was active against CD138+ primary MM cells and displayed a synergistic inhibition effect with bortezomib. Collectively, our data suggested that SL1 could be beneficial as a c‐met targeted antagonist in MM.

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“…Pegaptanib (marketed as Macugen) is FDA approved RNA aptamer that can inhibit VPF and used as anti-angiogenesis macular degeneration [25]. Subsequently, Pegaptanib was considered for cancer therapy [26]. Keratinocyte growth factor is responsible for facilitating epithelium formation and helps in healing.…”

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confidence: 99%

Aptamer: A Novel Therapeutic Oligonucleotide

Patel¹

2017

JNMR

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The aptamer is an oligonucleotide which is a short version of biological nucleic acids (such as DNA and RNA) with defined sequence of nucleotides. Based on the complexity of molecule, the aptamers lies in-between protein molecules and small chemical molecules. Aptamers have high specificity and affinity towards target proteins. They are screened from random sequences of oligonucleotides based on the highest affinity for target proteins using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Researchers have discovered various applications of aptamers that are ready to replace the therapeutic use of biological proteins (such as antibodies) that have complexity in manufacturing and characterization. The present review describes the structural modification in aptamers such as PEGylation, substitution of functional groups, use of an enantiomeric oligonucleotide and its applications. Aptamers can be deactivated, when needed, by the use of reversal agent that contains oligonucleotide sequence complementary to aptamers. This property of aptamers makes them potential therapeutic from a safety point of view. In recent scenario, aptamers are developed for targeted drug delivery systems by conjugating with drug molecules or delivery vesicles such as liposomes. ' Anti-sense Aptamers' are being developed to silent the expression of genes responsible for the proliferative growth of tissue in cancer. Other applications of aptamers such as environmental monitoring and laboratory testing are also described in this review. Keywords: IntroductionBiotechnology based products are incredibly capturing market shares day by day. Chemistry based synthesis has a limitation when we talk about the tertiary and quaternary structure of large molecules such as protein. The human body is functioning by different biochemical reactions. Protein molecules are broadly involved in every aspect of the biological reaction. In the current paradigm, such functional proteins get expressed in microorganism by genetic variation as a part of the upstream process. Subsequently, these proteins are separated from the microorganisms and purified (as a downstream process) retaining its biological activity to inject in the human body. These complex proteins are difficult to cultivate, separate, characterize and reproduce [1,2].The basic mechanism of protein synthesis in any of the living organism involves transcription and translation of polynucleotide chain of Adenine, Guanine, Thymine, and Cytosine [3]. The sequence of the oligonucleotide is responsible for translating specific protein using a specific sequence of amino acid involved in the synthesis of protein. Currently marketed protein formulations readily provide biological action at the target site when injected into the body. Such protein molecules are produced outside of the human body and injected in purified and active form. However, the stability of proteins is the major concern in the development of protein formulations. Such biological molecules have a tertiary and qua...

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Aptamers: A promising chemical antibody for cancer therapy

Cited by 89 publications

References 128 publications

Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts

Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts

Targeting c‐met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma

Aptamer: A Novel Therapeutic Oligonucleotide

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