Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer

Wu, Xiaoqiu; Shaikh, Atik Badshah; Yu, Yuanyuan; Li, Yongshu; Ni, Shuaijian; Lu, Aiping; Zhang, Ge

doi:10.3390/ijms18091851

Cited by 35 publications

(29 citation statements)

References 152 publications

(176 reference statements)

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“…In America, approximately 230,000 women are diagnosed with breast cancer annually [2]. Although the identification of the molecular types and the improvement of standard therapy specific to breast cancer types have ameliorated patients' survival outcomes [3,4], effective treatment strategies are yet to be developed in some types of breast cancer patients, such as triple-negative breast cancer. Further, the incidence of both posttreatment recurrence and distant organ metastasis and breast cancer-related death remains high [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

HCK can serve as novel prognostic biomarker and therapeutic target for Breast Cancer patients

Zhu¹,

Zhang²,

Bai³

et al. 2020

Int. J. Med. Sci.

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The role of HCK expression in the prognosis of breast cancer patients is unclear. Thus, this study aimed to explore the clinical implications of HCK expression in breast cancer. We assessed HCK expression and genetic variations in breast cancer using Oncomine, GEPIA, UALCAN, and cBioPortal databases. Then, immunochemistry was used to analyze HCK expression in breast cancer specimens, non-cancer tissues and metastatic cancer tissues. Consequently, we evaluated the effect of HCK expression on survival outcomes set as disease-free survival (DFS) and overall survival (OS). Finally, STRING, Coexpedia, and TISIDB database were explored to identify the molecular functions and regulation pathways of HCK. We found that breast cancer tissues have more HCK mRNA transcripts than non-cancer tissues. Patients with HCK expression had significantly shorter DFS and OS. The ratio of HCK expression was higher in cancer tissues than in non-cancer tissues. These results from STRING database, FunRich software, and TISIDB database showed that HCK was involved in mediating multiple biological processes including immune response-regulating signaling pathway, cell growth and maintenance through multiple signaling pathways including epithelial to mesenchymal transition, PI3K/AKT signaling pathway, and focal adhesion. Overall, HCK may be an oncogene in the development of breast cancer and thus may as a novel biomarker and therapeutic target for breast cancer.

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Section: Introductionmentioning

confidence: 99%

HCK can serve as novel prognostic biomarker and therapeutic target for Breast Cancer patients

Zhu¹,

Zhang²,

Bai³

et al. 2020

Int. J. Med. Sci.

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“…This is in part due to their small size, which minimizes potential toxicity that might be caused by excess aptamers or their conjugates. On the other hand, the small size (averages between 5-15 kDa) of aptamers may also be a disadvantage for in vivo use, where renal filtration may occur before the aptamer can reach its intended target site (Catuogno and Esposito, 2017;Wu et al, 2017). In contrast, conventional mAbs are much larger in size compared to aptamers, resulting in longer circulation times in vivo, and reduced internalization capability.…”

Section: (B)mentioning

confidence: 99%

“…Conjugation of aptamers to larger molecules (most commonly polyethylene glycol-PEG) can however extend the circulation time of aptamers in vivo, although this increased ability to remain within the circulatory system may unfortunately ultimately be a disadvantage, as aptamers, especially those made of RNA, are susceptible to nuclease degradation. Chemically modified aptamers are however relatively easy to produce and can reduce vulnerability to nucleases in vivo (Wu et al, 2017).…”

Section: (B)mentioning

confidence: 99%

Internalized Functional DNA Aptamers as Alternative Cancer Therapies

Marshall

Wagstaff

2020

Front. Pharmacol.

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Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular signalling pathways following receptor binding, or via internalization and targeting to specific subcellular compartments. DNA aptamers represent a promising molecular tool in this arena that can be used for both specific cell surface targeting and subsequent internalization and can also elicit a functional effect upon internalization. This review examines various cancer targeting cellinternalizing aptamers, with a particular focus towards functional aptamers that do not require additional conjugation to nanoparticles or small molecules to elicit a biological response. With a deeper understanding and precise exploitation of cancer specific molecular pathways, functional intracellular DNA aptamers may be a powerful step towards more widespread development of precision therapeutics.

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“…Shows good tumor penetration due to its small size (3000-20 000 Da), but comparably less efficient than small molecule targeting ligands. 136…”

Section: Penetration and Uptake In Tumor Tissuesmentioning

confidence: 99%

Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer

et al. 2019

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Background Prostate‐specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well‐characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000‐fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA‐targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers. The targeting moieties are either conjugated to radionuclear isotopes or near‐infrared agents for efficient diagnosis of PCa. Recent findings From the analysis, it was found that several small molecule–derived PCa imaging agents are approved for clinical trials in Europe and the United States, and few are already in the clinical use for diagnosis of PCa. Even though 111In‐labeled capromab pendetide was approved by the Food and Drug Administration (FDA) and other engineered antibodies are available for detection of PCa, but high production cost, low shelf life (less than 1 month at 4°C), possibility of human immuno reactions, and low blood clearance rate necessitated a need for developing new imaging agents, which are serum stable, cost‐effective, and possesses longer shelf life (6 months), have fast clearance rate from nontargeted tissues during the diagnosis process. It is found that small molecule ligand‐derived imaging agents possesses most of the desired properties expected for an ideal diagnostic agent when compared with other targeting moieties. Conclusion This report discusses in detail the homing moieties used in the development of targeted diagnostic tools for detection of PCa. The merits and demerits of monoclonal antibodies, small molecule ligands, peptides, and aptamers for imaging of PCa and intraoperative guided surgery are extensively analyzed. Among all, urea‐based ligands were found to be most successful in preclinical and clinical trials and show a major promise for future commercialization.

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Potential Diagnostic and Therapeutic Applications of Oligonucleotide Aptamers in Breast Cancer

Cited by 35 publications

References 152 publications

HCK can serve as novel prognostic biomarker and therapeutic target for Breast Cancer patients

HCK can serve as novel prognostic biomarker and therapeutic target for Breast Cancer patients

Internalized Functional DNA Aptamers as Alternative Cancer Therapies

Comparison of prostate‐specific membrane antigen ligands in clinical translation research for diagnosis of prostate cancer

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