FGFR expression and susceptibility to an FGFR inhibitor

A FGFR2, FGFR1 technology, applied in the field of FGFR expression and sensitivity to FGFR inhibitors

Inactive Publication Date: 2018-05-11
DEBIOPHARM INTERNATIONAL SA
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Answers to these questions may be inhibitor-specific

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
  • FGFR expression and susceptibility to an FGFR inhibitor
  • FGFR expression and susceptibility to an FGFR inhibitor
  • FGFR expression and susceptibility to an FGFR inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0147] Example 1: In Vivo Efficacy of Compound A in Gastric PDX Model Correlates with FGFR2 Expression and / or Amplification

[0148] Considering their GCN and FGFR2 expression levels and FGFR2 fusions, 11 gastric cancer PDX models were selected, thus constituting a balanced model set with FGFR2 expression levels as evenly distributed as possible.

[0149]For each tumor model, the effect of Compound A on tumor growth (treatment efficacy), FGFR copy number, and FGFR mRNA levels was assessed (or reassessed). Tumor fragments were harvested from seeded mice inoculated with selected PDX tumors and used to inoculate female Balb / c nude mice. One tumor fragment (2-3 mm in diameter) was inoculated subcutaneously on the right side per mouse for tumor development. When the average tumor size reaches about 200-250mm 3 start treatment. Compound A (60-80 mg / kg) formulated as a suspension in 1% Kollidon VA64 in deionized water or vehicle alone (i.e., 1% Kollidon VA64 in deionized water) wa...

Embodiment 2

[0166] Example 2: In Vivo Efficacy of Compound A in Esophageal Squamous Cell Carcinoma (ESCC) PDX Model Correlates with FGFR1 Expression and / or Amplification

[0167] Taking into account their GCN and FGFR1 expression levels, 13 ESCC PDX models were selected, thus constituting a balanced model set with FGFR1 expression levels as evenly distributed as possible. FGFR1 fusions have not been reported in this specific ESCC indication.

[0168] For each tumor model, the effect of Compound A on tumor growth (treatment efficacy), FGFR copy number, and FGFR mRNA levels was assessed (or re-evaluated). Tumor fragments were harvested from seeded mice inoculated with selected PDX tumors and used to inoculate female Balb / c nude mice. One tumor fragment (2-3 mm in diameter) was inoculated subcutaneously on the right side per mouse for tumor development. When the average tumor size reaches about 200-250mm 3 start treatment. Compound A (60-80 mg / kg) formulated as a suspension in 1% Kollido...

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

A method of selecting a subject suffering from a cancer for a therapeutic regimen of administration of a pharmaceutical composition comprising an effective amount of an FGFR inhibitor is described. The method comprises (1) the taking of a tumor or liquid biopsy from the subject; (2) determination of the level of expression of any or all of FGFR1, FGFR2 and FGFR3, and (3) comparison of the determined level of expression of at least one of FGFR1, FGFR2 and FGFR3 with a pre-established threshold value, and declaring the subject eligible for the therapeutic regimen if the determined level exceedsthe threshold value. The invention also relates to a method of personalized cancer therapy comprising selection of a subject by the above-described method and subjecting the subject to a therapeutic regimen that comprises administration of a pharmaceutical composition comprising an effective amount of an FGFR inhibitor.

Description

technical field [0001] The present invention relates to the selection of a subject having a tumor for treatment with an FGFR inhibitor, and to the treatment of such a subject with such an inhibitor. Background technique [0002] Fibroblast growth factor and its receptor (FGFR) drive important developmental signaling pathways affecting cell proliferation, migration and survival. Aberrant FGF signaling plays a role in many cancers. Turner, N. and Grose, R. (2010) Nat. Rev. Cancer 10:116-29. The FGFR family consists of FGFR1, FGFR2, FGFR3 and FGFR4. FGFRs are tyrosine kinases that are activated in a subset of tumors by gene amplification, mutation, or chromosomal translocations or rearrangements. Amplification of FGFR1 occurs in squamous cell lung cancer and estrogen receptor-positive breast cancer. FGFR2 is also amplified in gastric and breast cancers. FGFR2 mutations have been observed in endometrial cancer and FGFR3 mutations in bladder cancer. The Cancer Genome Atlas ...

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): C12Q1/6886
CPCC12Q2600/106C12Q2600/158C12Q1/6886G01N33/57407G01N2800/52G01N2333/71C12Q1/6806C12N15/00C12Q2600/112C12Q2600/118C12Q2600/156
Inventor 安妮·瓦兰-谢塞克斯科琳·穆隆弗兰克·布里绍里安娜·波科尔斯卡-博奇
Owner DEBIOPHARM INTERNATIONAL SA
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