Screening method for anti-tumor medicine biomarker and application of anti-tumor medicine biomarker

A technology of anti-tumor drugs and biomarkers, applied in the field of tumor treatment, can solve the problems of non-recording algebra, noise, unclear algebra, etc., to improve efficiency and ability, reduce the impact of noise, and achieve the effect of small differences

Active Publication Date: 2015-10-14
思路迪科技(上海)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When carrying out such research, a major problem is that there are often a large number of differences in the genome of cells with different sensitivities to the same drug. Some of these differences may be related to drug responses, while more are are differences that are not associated with drug response, and these differences add irreducible noise to the correlation analysis, making marker analysis difficult
In addition, many of the existing commercial cell lines are exchanged and used by laboratories all over the world, and the algebra is basically not recorded and the algebra is not clear

Method used

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  • Screening method for anti-tumor medicine biomarker and application of anti-tumor medicine biomarker
  • Screening method for anti-tumor medicine biomarker and application of anti-tumor medicine biomarker
  • Screening method for anti-tumor medicine biomarker and application of anti-tumor medicine biomarker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0188] Example 1 Establishment of Liver Cancer Tumor Cell Line Collection and Chromosome Identification

[0189] After the solid tumor was isolated from multiple regions of the orthotopic tumor tissue of a liver cancer patient, a primary liver cancer cell line OPP containing 26 strains that can be stably passaged was successfully established after multiple times of defibrosis treatment and subculture. The cell name numbers are HCC307 2-1#, HCC307 2-2#, HCC307 2-3#, HCC307 2-4#, HCC307 2-5#, HCC307 5-1#, HCC307 5-3#, HCC307 7- 2#, HCC307 7-3#, HCC307 7-4#, HCC307 7-7#, HCC307 7-9#, HCC307 11-5#, HCC307 11-8#, HCC307 12-1#, HCC307 12-2# , HCC307 12-3#, HCC307 12-4#, HCC307 12-5#, HCC307 12-6#, CC307 12-7#, HCC307 13-1#, HCC307 13-4#, HCC307 13-6#, HCC307 14-1#, HCC307 14-2#.

[0190] Observed from the cell morphology, the 26 cell lines all showed epithelial morphology (one representative cell line was as follows: figure 2 shown). After identification by karyotype analysis, ...

Embodiment 2

[0195] Example 2 Genome Sequencing

[0196] The gene expression profile, CNV copy number and exon sequencing of the 26 cell lines established in Example 1. The results of the data show that the genomes of these cell lines from the same subject have a high degree of homology, and there are also certain differences in gene expression, CNV copy number variation and exon variation. As shown in the figure, by comparing the CNV differences between cell lines, the CNV copy numbers among the 26 cell lines in OPP-HCC307 are not completely consistent, and there are differences, but the differences between them are significantly smaller than those from different subjects. Liver cancer cell lines (P=1.0953e-260, image 3 ).

[0197] image 3 It shows the evaluation of the distance between any two cell lines from different sources (including 26 OPP-HCC307 cell lines and 27 hepatoma cell lines from CCLE) using gene-based CNV data.

[0198] in image 3 A shows the heat map of (1-distanc...

Embodiment 3

[0199] Example 3 Antitumor Drug Sensitivity Test

[0200] Antitumor drug sensitivity tests were performed on the cell line collection obtained in Example 1. In the present embodiment, the antineoplastic drugs adopted are as follows:

[0201] Targeted drugs: 17-AAG, 2-deoxyglucose, Abiraterone, ABT-263, AC-220, AT-406, AZD4547, AZD5363, AZD7762, BI-2536, Birinapant, BMS-754807, Bortezomib (Bortezomib), BX-795, Cabozantinib, CAL-101, Carfilzomib, Crizotinib, Danusertib, Dasatinib, Dovitinib, Elesclomol, Embelin, Entinostat (MS-275), Enzastaurin, Everolimus, Foretinib, Fulvestrant, Ganetespib, GDC0941, GSK429286A, JQ1, KU-55933, KX2-391 , Lenvatinib, Linifanib, Linsitinib, LY2157299, Masitinib, MK-1775, MK-2206, MLN-4924, Neratinib, NU7441, Nutlin-3, NVP-BEZ235, NVP-BKM120, Oratinib, PCI-32765, PD-0325901, PD -0332991, PD-173074, PH-797804, PRT062607, R-406, Refametinib, Regorafenib, SCH900776, sgi-1776, Sorafenib, Sunitinib, TAE684 , Temsirolimus, TG-101348, Tideglusib, Tipi...

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Abstract

The invention discloses a screening method for an anti-tumor medicine biomarker and an application of the anti-tumor medicine biomarker. Particularly, the method comprises the following steps: (a) providing tumor cells as initial cells, wherein the tumor cells are from the same tumor tissues of the same object; (b) carrying out passage and establishment on the initial cells, and carrying out genome information detection on the obtained cell line, so as to obtain at least five tumor cell lines which are different in genome and highly homologous; (c) carrying out anti-tumor medicine sensitivity test on the tumor cell lines obtained from the step (b), and parting the tumor cell lines based on the sensitivity of the anti-tumor medicine; and (d) analyzing the genome information of the tumor cell lines based on the parting result, so as to determine the anti-tumor medicine biomarker. According to the method disclosed by the invention, the background noise between different tumor cell lines can be reduced to the maximal extent to contribute to efficient and accurate screening of the anti-tumor medicine biomarker.

Description

technical field [0001] The present invention relates to the field of tumor therapy. Specifically, it relates to a method for screening antitumor drug biomarkers. Background technique [0002] The efficacy of anticancer drugs is mainly determined by the abnormal expression of their genomes. Due to the instability of tumor genomes and the heterogeneity among tumors, anticancer drugs are often only effective in a certain group of patients. For example, Gleevec, which targets BCR-Abl, has a five-year survival rate of more than 90% in patients with chronic myelogenous leukemia with BCR-ABL fusion expression, and Iressa, which targets EGFR, is successfully used in non-small cell lung cancer with EGFR mutations , ALK inhibitor Crizotinib is only approved for ALK-positive patients. Under the indications of biomarkers such as BCR-ABL fusion, EGFR mutation, and ALK fusion, "effective population" and "ineffective population" can be effectively judged, thereby improving efficacy and r...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/02C12Q1/68C12N5/09
Inventor 熊磊
Owner 思路迪科技(上海)有限公司
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