An RNA Aptamer Targeting the Receptor Tyrosine Kinase PDGFRα Induces Anti-tumor Effects through STAT3 and p53 in Glioblastoma

Yoon, Sorah; Wu, Xiwei; Armstrong, Brian; Habib, Nagy; Rossi, John J.

doi:10.1016/j.omtn.2018.11.012

Cited by 40 publications

(20 citation statements)

References 70 publications

(80 reference statements)

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“…Aptamers have also emerged as useful targeted delivery agents for conventional drugs and small RNAs including siRNAs and miRNAs due to several advantages, such as small physical size, high stability and low immunogenicity [ 137 ]. Recently, STAT3 silencing by aptamer-siRNA chimera obtained excellent inhibition in the therapy of glioblastoma [ 138 , 139 ], suggesting that the improved oligonucleotides might offer translational potential for the treatment of solid tumors.…”

Section: Targeting Stat3 For Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 is broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors. Therefore, targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers. In this review, we outline the importance of STAT3 signaling pathway in tumorigenesis and its immune regulation, and highlight the current status for the development of STAT3-targeting therapeutic approaches. We also summarize and discuss recent advances in STAT3-based combination immunotherapy in detail. These endeavors provide new insights into the translational application of STAT3 in cancer and may contribute to the promotion of more effective treatments toward malignancies.

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Section: Targeting Stat3 For Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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“…The improved half‐life of aptamers in vivo is suggestive of future clinical application as molecular imaging agents . Of note, aptamers themselves can be used as therapeutics in blood clotting, or local treatment, or inducing antitumor effect . Furthermore, aptamer‐mediated delivery systems have been broadly applied in cancer therapies, including aptamer‐drug conjugates, aptamer‐nanoparticle/polymer‐drug delivery system, and aptamer‐mediated cancer nucleic acid therapy .…”

Section: Aptamer Emerges As a Prominent Targeting Ligand For Nanodelimentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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Intense efforts from both scientists and physicians across Australia have been devoted onward advancing studies to fill the gap in understanding the biology and pathogenesis underlying cancer development. Exosomes are membrane-bound bio-nanoparticles secreted or released by most cells into the extracellular space. There has been an increasing interest in such bio-nanoparticles over the past 10 years, evident from the publication number of only 324 papers in 2006 to a massive increase to 4603 publications in 2018 with the search term "exosome" based on title/abstract in PubMed. Among these studies, 151 articles published from 2007 to 2018 are from Australian institutions, with 33 papers published in 2018. Such a strong surge of interest is due to discoveries that exosomes play key roles in intercellular and intertissue communication mediated by virtue of cargos contained inside the membrane-confined space. Furthermore, exosome cargos, including proteins, mRNAs and miRNAs, are linked to the Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally derived 50-150 nm nanovesicles that play important roles in cell-to-cell and/or cell-to-tissue communications and cross-species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human-derived nanovesicles are summarized.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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“…In the first, the STAT3 siRNA was conjugated to PDR3, an anti-PDGFRα RNA aptamer. The conjugate strengthens the effect of the aptamer alone: in fact, the authors firstly demonstrated the effect of PDR3 on apoptosis and then confirmed that PDR3-siSTAT3 mediates strong reduction in cell viability in vitro [ 42 ]. In the second, Esposito et al characterized a modified 2′F-Py nuclease-resistant RNA conjugate in vitro and in vivo.…”

Section: Resultsmentioning

confidence: 99%

The Role of RNA and DNA Aptamers in Glioblastoma Diagnosis and Therapy: A Systematic Review of the Literature

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et al. 2020

Cancers

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Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional structures of single-stranded nucleic acids (RNA or DNA), identified by an in vitro process, named systematic evolution of ligands by exponential enrichment (SELEX), starting from a partially random oligonucleotide library. They bind to a molecular target with high affinity and specificity and can be easily modified to optimize binding affinity and selectivity. Thanks to their properties (low immunogenicity and toxicity, long stability, and low production variability), a large number of aptamers have been selected against GBM biomarkers and provide specific imaging agents and therapeutics to improve the diagnosis and treatment of GBM. However, the use of aptamers in GBM diagnosis and treatment still represents an underdeveloped topic, mainly due to limited literature in the research world. On these bases, we performed a systematic review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for GBM diagnosis and treatment. Thirty-eight studies from 2000 were included and investigated. Seventeen involved the use of aptamers for GBM diagnosis and 21 for GBM therapy. Our findings showed that a number of DNA and RNA aptamers are promising diagnostic and therapeutic tools for GBM management.

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An RNA Aptamer Targeting the Receptor Tyrosine Kinase PDGFRα Induces Anti-tumor Effects through STAT3 and p53 in Glioblastoma

Cited by 40 publications

References 70 publications

Targeting STAT3 in Cancer Immunotherapy

Targeting STAT3 in Cancer Immunotherapy

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

The Role of RNA and DNA Aptamers in Glioblastoma Diagnosis and Therapy: A Systematic Review of the Literature

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