Supercharge Your Innovation With Domain-Expert AI Agents!

Application of Selumetinib to treatment of gastric cancer resistant to HER2 targeted treatment

A technology of selumetinib and targeted therapy, applied in the field of biomedicine, can solve the problems of insufficient objective effective rate in patients with gastric cancer

Active Publication Date: 2018-07-20
SUN YAT SEN UNIV CANCER CENT
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, most patients who are sensitive to trastuzumab develop drug resistance within one year after starting the drug; the objective effective rate of trastuzumab combined with chemotherapy in patients with gastric cancer is still very low
Currently, for the treatment of HER2-positive gastric cancer, there is no way to overcome drug resistance after trastuzumab resistance

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of Selumetinib to treatment of gastric cancer resistant to HER2 targeted treatment
  • Application of Selumetinib to treatment of gastric cancer resistant to HER2 targeted treatment
  • Application of Selumetinib to treatment of gastric cancer resistant to HER2 targeted treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 In vitro experiment shRNA interferes with the expression of NF1 to reduce the sensitivity of HER2-positive gastric cancer cells (NCI-N87 and SNU-216) to trastuzumab and lapatinib

[0035] 1. First, use lentivirus to silence NF1 expression in two HER2-positive gastric cancer cell lines (NCI-N87 and SNU-216). The result is as figure 1 , NF1 expression was successfully suppressed.

[0036] 2. The above-mentioned gastric cancer cell line was treated with the same concentration of Trastuzumab (Trastuzumab, a monoclonal antibody against HER2). The results showed that NF1 low expression cell lines were resistant to trastuzumab ( figure 2 ).

[0037] 3. The same results can be obtained after treatment with the small molecule HER2 inhibitor lapatinib (lapatinib) ( figure 2 ), indicating that downregulation of NF1 mediated the resistance of cancer cells to lapatinib.

Embodiment 2

[0038] Example 2 Effect of NF1 silencing on downstream signaling pathways

[0039] 1. After silencing NF1 expression as described in Example 1, detect the phosphorylation levels of PI3K / AKT and MEK / ERK (both are key molecules in the downstream signaling pathway of HER2) by Western blot.

[0040] The results showed that the phosphorylation levels of PI3K / AKT and MEK / ERK were significantly increased (eg image 3 ), indicating that shRNA interference with NF1 can enhance the activation of downstream PI3K / AKT and RAS / RAF / MEK / ERK signaling pathways, and AKT and ERK signaling molecules are involved in NF1-mediated resistance to HER2-targeted therapy.

Embodiment 3

[0041] Example 3 Lapatinib combined with selumetinib (Selumetinib, AZD6244) overcomes drug resistance of HER2-positive gastric cancer to HER2-targeted lapatinib

[0042] 1. Experimental method

[0043] MTT colorimetric analysis method is used in cytotoxicity experiments, select stably transfected NCI-N87-NC, NCI-N87-NF1-sh#1, NCI-N87-NF1-sh#2 and SNU-216-NC, SNU- 216-NF-1-sh#1 and SNU-216-NF-1-sh#2 cells were added with lapatinib (0.2 μM, cultured for 24 hours), selumetinib (1 μM, cultured for 24 hours) and Cytotoxicity experiments were performed with lapatinib (0.2 μM) combined with selumetinib (1 μM). The relative absorbance (OD) was measured at a wavelength of 570 nm using an OPSYS microplate Reader (DYNEX Technologies, Inc. (Chantilly, VA)) instrument. The experiment was repeated 3 times, and the mean (mean) and standard deviation (SD) were calculated. According to the absorbance value, calculate the half inhibitory rate (IC50) of the drug on the cells, that is, the dru...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses application of Selumetinib (AZD6244) to treatment of gastric cancer resistant to HER2 targeted treatment. The resistance of the NF1-deleted HER2 positive gastric cancer to theHER2 targeted treatment (including Trastuzumab monoclonal antibody medicine resistance and lapatinib medicine resistance) is found through research; the obvious curative effect is realized on medicineresistant HER2 positive gastric cancer; the Selumetinib can be applied to the treatment aspect of the medicine resistant HER2 positive gastric cancer; the problem of the medicine resistance of the gastric cancer to the HER2 is solved. The invention provides novel application and a novel application field for the Selumetinib, and also provides a novel treatment method for the treatment of the medicine resistant HER2 positive gastric cancer; in addition, the Selumetinib is the clinic application method and has good popularization and application prospects.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to the application of selumetinib in the treatment of gastric cancer resistant to HER2-targeted therapy. Background technique [0002] Gastric cancer is a malignant tumor originating from the epithelium of the gastric mucosa. It ranks first in the incidence of various malignant tumors in my country and seriously endangers human health. [0003] Trastuzumab, a humanized monoclonal antibody against HER2, has been successfully used to treat stage IV gastric cancer with HER2 overexpression. [0004] However, most patients who are sensitive to trastuzumab develop drug resistance within one year after starting the drug; the objective effective rate of trastuzumab combined with chemotherapy in patients with gastric cancer is still very low. At present, for the treatment of HER2-positive gastric cancer, there is no way to overcome drug resistance after trastuzumab resi...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/4184A61K31/517A61P35/00
CPCA61K31/4184A61K31/517A61K2300/00
Inventor 徐瑞华王德深刘泽先鲁运新
Owner SUN YAT SEN UNIV CANCER CENT
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com