Aptamer Targeting the ERBB2 Receptor Tyrosine Kinase for Applications in Tumor Therapy

Aptamers are an emerging class of molecules in cancer therapy. They can be easily synthesized and are considered cost-effective drug candidates. In this book chapter we describe the selection and characterization of DNA aptamers specific to the human epidermal growth factor receptor 2 (ERBB2/HER2), an oncogenic tyrosine kinase. First, a DNA aptamer library is applied and ERBB2-specific aptamers are selected using SELEX. Binders are subcloned into a pGEM-T vector, sequenced, and characterized using biochemical and cell biological techniques. By multimerizing the selected ERBB2 aptamers, it might be possible to significantly increase their avidity. For example, we could show that a trimeric ERBB2-specific aptamer could efficiently internalize membranal ERBB2. Furthermore, the receptor assembled in cytoplasmic puncta and was finally degraded by the lysosome. In addition, the selected, trimeric aptamer inhibited proliferation in an XTT assay in comparison to a control sequence. Aptamers selected using the protocol we describe might exert anticancer effect. In our example of a trimeric anti-HER2 aptamer, we could report that a human gastric xenograft mouse model demonstrated pharmacological value of the selected aptamer in vivo. This chapter should enable the interested reader to replicate selection of DNA aptamers specific to oncogenic cell surface. We would like to particularly emphasize some experimental approaches which were used to further characterize selected aptamer sequen...
Source: Springer protocols feed by Cancer Research - Category: Cancer & Oncology Source Type: news

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Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment. Introduction Metastasis is the leading cause of breast cancer mortality, which has been one major challenge in clinical treatment (1). In particular, triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptors (ER), progesterone receptors (PR) and HER2 receptors, which is one of the most aggressive types of breast cancers, marked by high rates of relapse, visceral metastases and early death (2, 3). The...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Recombinant cucurmosin-based immunotoxin targeting HER-2 with potent in vitro anti-cancer cytotoxicity. Biochem Biophys Res Commun. 2019 Mar 25;: Authors: Xiong J, Zhang C, Wu S, Gu X, Cai Y, Xu C, Chen Z, Sun J, Wu X, You X, Huang Z, Xie J Abstract Trastuzumab is a humanized monoclonal antibody against HER2 approved by FDA for breast and gastric cancer therapy. However, only a quarter of patients have the potential to benefit from it, and most of them develop resistance within therapy. The main purpose of this study is to broaden trastuzumab's therapeutic window by conjugating trastuzumab with r...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Abstract HER2 is a member of epidermal factor receptor (EGFR) family which is overexpressed in breast cancer, ovarian cancer and gastric cancer. Development of new binders for cancer cell surface receptors and expressing them at the surface of exosomes would be a great approach in targeted cancer therapy. We found a high affinity scFv against HER2 using ribosome display with the approach of applying it as a targeting moiety at the surface of exosomes by fusion to lysosomal associated membrane protein 2B (LAMP2B). We also provide some structural information about the ribosome display selected scFv (scFv HFS2) throu...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
We present the case of a patient diagnosed with a de novo metastatic gastric cancer who experienced an extraordinary long response to multiple lines of chemotherapy (FOLFOX6, paclitaxel plus ramucirumab, FOLFIRI, rechallenge with FOLFOX6).Key Message: Gastric cancer therapy should be considered as the result of a strategy based on the patient ’s condition, and tolerance and response to various therapies. The emerging evidence of the role of subsequent lines of therapy, along with the recognition of the pivotal role of nutritional support and the availability of new drugs, should help clinicians in the management of p...
Source: Gastrointestinal Tumors - Category: Gastroenterology Source Type: research
In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S‐1 can substitute capecitabine or 5‐FU when specific toxicities are encountered.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Cancer Therapy and Prevention Source Type: research
Conclusions: Taken together, the results provide insight into the biological and clinical potential of targeted AMO-21 and 5-Fu co-delivery using modified trastuzumab for GC treatment.Cell Physiol Biochem 2017;44:2158 –2173
Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
In conclusion, the efficacy of DS‐8201a as a treatment for patients with T‐DM1‐resistant breast or gastric cancer merits investigation.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Cancer Therapy and Prevention Source Type: research
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