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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Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and motility. We previously reported cross-talk between GPNMB and human epidermal growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might play an important role in resistance to anti-HER2 therapy in breast cancer. Here, we clarified the association between GPNMB and HER-family proteins in gastrointestinal cancer by examining their relationships using gastric and colorectal cancer cell lines. We found that GPNMB depletion of by small-interfering RN...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Introduction: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLT) including patients with early and advanced gastric cancer. However, it is unknown the prognostic impact in patients with HER2-positive metastatic gastric cancer.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
The human epidermal growth factor receptor 2 (HER2) involved proliferation, angiogenesis, and reduced apoptosis in gastric cancer (GC), which is a common target for tumor therapy. HER2 is usually overexpressed...
Source: Journal of Translational Medicine - Category: Research Authors: Tags: Research Source Type: research
Conditions:   Gastric Cancer;   HER2 Overexpressing Gastric Carcinoma Intervention:   Drug: RC48-ADC Sponsor:   RemeGen Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
In conclusion, HER2-targeted AuNPs with conjugated Tmab is a promising strategy for the development of novel therapeutic agents to overcome Tmab resistance in gastric cancer. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
Abstract BACKGROUND: Gastroesophageal cancers are often grouped together even though cancers that originate in the esophagus often exhibit different histological features, geographical distribution, risk factors, and clinical characteristics than those originating in the stomach. Herein, we aimed to compare the molecular characteristics of three different gastroesophageal cancer types: esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC). SUBJECTS, MATERIALS, AND METHODS: In total, 3,342 gastroesophageal cancers were examined. Next-generation sequencing ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Conclusion: HER2 positivity was noted in 23% of the cases. 23.4% of intestinal type and 21.7% of diffuse type were HER2 positive. HER2 positivity did not significantly depend on age, gender, tumour type, grade and stage. Hence, HER2 remains as an independent biomarker and should be tested in all patients of gastric cancer regardless of the clinicopathological findings for offering a personalized treatment. PMID: 29802704 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
Tyrosine kinase receptors (TKRs) play critical roles in gastric cancer (GC) progression, and have a potential to be targets for novel molecular targeted agents. In the process of patient selection for molecular target agents, targeted biopsy under endoscopic observation is the first step. However, heterogeneous expression of TKRs through the macroscopic appearance in GC has not been extensively addressed.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Saturday abstract Source Type: research
AbstractThe effects of different patient factors and dose levels of chemotherapeutic agents on clinical outcomes in advanced gastric cancer are not as yet fully characterized. We aimed at developing an integrative model that incorporates dose and covariate information to predict tumor growth and patient survival in advanced gastric cancer patients treated with trastuzumab (T), 5-FU(F)/capecitabine (X) (F or X), and cisplatin (P). Sixty-nine patients (training dataset) were used for model building and a separate 86 patients (test dataset) for model validation. A fraction of tumor cells sensitive to each drug was incorporate...
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research
AbstractSB3 (Ontruzant®) is the first biosimilar of the reference anti-HER2 antibody trastuzumab to be approved in the EU. It is approved for use in all indications for which reference trastuzumab is approved, namely HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer. SB3 has similar physicochemical and pharmacodynamic properties to those of reference trastuzumab, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers and women with HER2-positive early or locally advanced breast cancer. SB3 demonstrated clinical efficacy considered equivalent to t...
Source: BioDrugs - Category: Drugs & Pharmacology Source Type: research
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