Method to predict or monitor the response of a patient to an ErbB receptor drug

A receptor, patient technology, applied in the field of gefitinib, can solve the problems of patient unpleasantness, difficulty, screening patient mutation detection, etc.

Inactive Publication Date: 2009-01-21
ASTRAZENCA UK LTD +1
View PDF6 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This is a difficult procedure, very unpleasant for the patient, and sometimes not feasible when the tumor is inoperable
[0006] Another problem with screening patients for mutations is the difficulty of detecting mutated genes among the plethora of wild-type genes

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
  • Method to predict or monitor the response of a patient to an ErbB receptor drug
  • Method to predict or monitor the response of a patient to an ErbB receptor drug
  • Method to predict or monitor the response of a patient to an ErbB receptor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 - Collection of Clinical Trials and Serum Samples

[0115] This study was conducted as a related study of a multicenter clinical phase II trial of gefitinib monotherapy. The conduct of this study was approved by the appropriate ethical review boards based on the recommendations of the Helsinki Statement for Biomedical Research Involving Human Subjects. Histological or cytological confirmation of chemotherapy in stage IIIB or IV- Japanese patients with NSCLC participated in this trial. All patients were given gefitinib orally at a fixed dose of 250 mg per day. Efficacy was assessed using the guidelines of "Response Evaluation Criteria in Solid Tumors (RECIST)" (J. Natl. Cancer Inst. 2000; 92: 205-216).

[0116] Twenty-eight patients were enrolled between October 23, 2002, and August 3, 2003 (Table 1). All patients were assessed for response, and their progression-free survival and overall survival were tracked. Blood samples (2 ml) from 27 patients were...

Embodiment 2

[0118] Embodiment 2-Utilize Scorpion primer and amplification retardation mutagenesis system (ARMS) to detect Detection of E746 A750 del and L858R EGFR mutations

[0119] EGFR Scorpion TM Sensitivity of the kit

[0120] The sensitivity of the EGFR Scorpion kit was evaluated through preliminary tests ( figure 1 ). When reaching a maximum of 45 cycles, the total curves of the E746_A750del standard DNA from 1 pg to 10,000 pg increased ( figure 1 a). When wild-type standard DNA and water were used as negative controls, the curve was not increasing and remained flat until reaching 50 cycles ( figure 1 a). Use diluted E746_A750del standard DNA and wild-type standard DNA at a ratio of 10 0 to 10 -5 , when a maximum of 45 cycles is reached, indicating the presence of a full curve growth of E746_A750del ( figure 1 b). The standard curve is linear over the range of measured quantities in this study, r 2 The values ​​are 0.997 and 0.987. The slopes of the two curves are al...

Embodiment 3

[0126] Example 3: EGFR mutation status in serum and impact on survival

[0127]Statistical analysis. Fisher's exact test was used to compare the presence of EGFR mutations in NSCLC patients with different characteristics, including gender, tumor type, and response to gefitinib. Regarding the analysis of response to gefitinib, according to RECIST criteria, patients were divided into two groups of partial response or stable disease (PR / SD) and progressive disease (PD). We compared Kaplan–Meier curves for overall survival and progression-free survival using standard log-rank tests. "Overall survival" (OS) was defined as the time from initiation of gefitinib administration to death from any cause; patients known to be alive at the time of analysis were examined at their last follow-up. "Progression-free survival (PFS)" was defined as the time from initiation of gefitinib to first occurrence of progressive disease or death from any cause; patients known to be alive and free of ...

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 provides a method for detecting ErbB receptor mutations comprising the steps of providing a bio-fluid sample from a patient; extracting DNA from said sample; and screening said DNA for the presence of one or more mutations that alter tyrosine kinase activity in the receptor.

Description

technical field [0001] The present invention relates to a method for predicting or monitoring a patient's response to ErbB receptor drugs, such as gefitinib targeting epidermal growth factor receptor (EGFR). This method provides sensitive and specific screening for genomic DNA mutations that occur at low concentrations in biological fluids such as serum. The method is suitable for detecting mutations known to increase ErbB tyrosine kinase receptor activity and which appear to be associated with response to ErbB receptor drug therapy. Background technique [0002] ErbB receptors are protein tyrosine kinases (TKs) belonging to the TK superfamily, members of which regulate signaling pathways that control cell growth and survival. The ErbB receptor family consists of four closely related subtypes: ErbB1 (epidermal growth factor receptor [EGFR]), ErbB2 (HER2 / neu), ErbB3 (HER3), and ErbB4 (HER4) (Cell. 2000; 103: 211-225). [0003] For example, signaling from EGFR is initiated ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/156C12Q1/6886C12Q2600/106A61P35/00A61P35/02A61P43/00C12Q1/485C12Q1/6858
Inventor K·尼施奥H基穆拉K·卡萨哈拉
Owner ASTRAZENCA UK LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap