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Novel biomarkers for susceptibility prediction associated with epidermal growth factor receptor-target agents and uses thereof

A use and receptor technology, applied in the field of new biomarkers for sensitivity prediction related to epidermal growth factor receptor-target preparations and its use, can solve the problem of weak results, and it is difficult to ensure a wide range of therapeutic agents and administration methods. Such problems, to achieve the effect of avoiding side effects

Active Publication Date: 2021-11-12
WELLMARKER BIO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] However, at present, remarkable results are still weak due to complex effects of factors related to biological reactions related to specific drugs, diversity of therapeutic agents and administration methods, and difficulty in securing a wide range of samples.

Method used

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  • Novel biomarkers for susceptibility prediction associated with epidermal growth factor receptor-target agents and uses thereof
  • Novel biomarkers for susceptibility prediction associated with epidermal growth factor receptor-target agents and uses thereof
  • Novel biomarkers for susceptibility prediction associated with epidermal growth factor receptor-target agents and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0188] Example 1. Activity of Epidermal Growth Factor Receptor Based on RON Protein Viability

[0189] 1-1. Existence of active form of RON protein in human colorectal cancer cell lines

[0190] The present inventors confirmed RON phosphorylation in a total of 19 human colorectal cancer cell lines by Western blotting in order to screen colorectal cancer cell lines in which RON protein was activated or inactive.

[0191] This phosphorylated RON protein is considered as RON active protein.

[0192] As a result, such as Figure 1a As shown, among the 18 types of cell lines, RON phosphorylated protein expression was observed in 4 cell lines (HT-29, KM12C, KM12L4, and SW1417), and it was found that 4 cell lines have RON activity.

[0193] On the other hand, in LoVo and Colo320HSR colorectal cancer cell lines, RON protein itself does not appear.

[0194] 1-2. Gene expression analysis based on RON protein activation by DNA microarray analysis

[0195] In order to analyze the gene ...

Embodiment 2

[0210] Example 2. Changes in human epidermal growth factor receptor activity based on whether RON activity is present

[0211] 2-1. Activation of epidermal growth factor receptor protein based on activation of RON protein

[0212] In order to confirm the activation of epidermal growth factor receptor protein by RON activation, the present inventors overexpressed the Δ160 gene, which is the active form of the RON gene, in the LoVo and Colo320HSR colorectal cancer cell lines that do not express RON, and then performed protein analysis. Blotting.

[0213] As a result, such as Figure 2a As shown, it was confirmed that the activity of activating the epidermal growth factor receptor by RON was increased.

[0214] 2-2. Changes in activity of epidermal growth factor receptor protein due to RON inhibition

[0215] In order to confirm the change in the activity of the epidermal growth factor receptor protein due to the activation of the RON protein, the present inventors artificiall...

Embodiment 3

[0220] Example 3. Drug sensitivity analysis of cetuximab based on activation of RON protein

[0221] 3-1. Endogenous intracellular binding analysis between RON protein and epidermal growth factor receptor protein

[0222] In order to analyze the binding between RON protein and epidermal growth factor receptor protein in the CaCO2 colorectal cancer cell line in an inactive state of RON and the KM12C colorectal cancer cell line in which RON is activated, the present inventors used RON antibody to Immunoprecipitation was used to observe whether the RON protein was combined with the epidermal growth factor receptor protein.

[0223] As a result, such as Figure 3a As shown, it can be seen that the RON protein binds to the epidermal growth factor receptor protein in CaCO2 cells without RON activity, while the RON protein binds to the epidermal growth factor receptor protein in KM12C cells with RON activity .

[0224] 3-2. Analysis of exogenous intracellular binding between RON p...

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Abstract

The present invention relates to novel biomarkers for predicting susceptibility to epidermal growth factor receptor-target preparations and uses thereof, provided in more detail as follows: Preparation-related sensitivity prediction biomarkers, including RON (Recepteur d'Origine Nantais) gene; epidermal growth factor receptor-target preparation-related sensitivity prediction composition, including gene expression levels for measuring the above-mentioned biomarkers Or the preparation of the expression or activity level of the protein of the above-mentioned gene; the composition for enhancing the sensitivity related to the epidermal growth factor receptor-target preparation, comprising the following inhibitor as an active ingredient: the above-mentioned inhibitor refers to the agent used to inhibit the above-mentioned gene An inhibitor that expresses or inhibits the expression or activity of a protein of the above-mentioned gene; a kit for predicting susceptibility related to an epidermal growth factor receptor-target preparation comprising the above-mentioned composition; and a susceptibility related to an epidermal growth factor receptor-target preparation method of prediction. According to the present invention, the sensitivity prediction effect of the present invention on the epidermal growth factor receptor-target agent in colon cancer is excellent, so the present invention can be usefully utilized in the treatment of colon cancer.

Description

technical field [0001] This invention was realized through the project number 1420030 under the support of the Korean Ministry of Health and Welfare. The research and management agency for the above-mentioned project is the Cancer Conquerment Promotion Research and Development Project Group. Development of Novel Therapeutics and Discovery of Biomarkers to Overcome Cetuximab Resistance in Patients with Colorectal Cancer", the competent authority is Seoul Asan Hospital, and the research period is from 2014.05.01 to 2017.04.30. [0002] The present invention is realized through the project number HI06C0868 under the support of the Ministry of Health and Welfare of Korea. The research and management agency of the above-mentioned topic is the Korean Health Industry Promotion Source, the Korean Health Industry Promotion Source, and the name of the research business is "Pilot Characterized Research Business". The title of the project is "Development of Innovative Anticancer Agents Ta...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/68C12Q2600/106C12Q2600/158C12Q1/6886A61P43/00A61P35/00A61K31/7088C12Q1/6844C12Q2600/118C12Q2600/156C12Q2600/178
Inventor 金太源陈东勋弘承祐文哉喜申在植金承美李大熙李银英李璱洪镕祥
Owner WELLMARKER BIO CO LTD