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1. WO2006101925 - BIOLOGICAL MARKERS PREDICTIVE OF ANTI-CANCER RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITORS

Publication Number WO/2006/101925
Publication Date 28.09.2006
International Application No. PCT/US2006/009403
International Filing Date 16.03.2006
IPC
G01N 33/574 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53Immunoassay; Biospecific binding assay; Materials therefor
574for cancer
G01N 33/74 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
74involving hormones
C12Q 1/48 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
48involving transferase
CPC
A61K 31/517
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
495having six-membered rings with two ; or more; nitrogen atoms as the only ring heteroatoms, e.g. piperazine ; or tetrazines
505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
517ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
A61P 35/04
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
04specific for metastasis
A61P 43/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
43Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
G01N 2800/52
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
52Predicting or monitoring the response to treatment; Prognosis
G01N 33/5011
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
48Biological material, e.g. blood, urine
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
5005involving human or animal cells
5008for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
5011for testing antineoplastic activity
Applicants
  • OSI PHARMACEUTICALS, INC. [US]/[US] (AllExceptUS)
  • GENENTECH, INC. [US]/[US] (AllExceptUS)
  • HALEY, John, D. [US]/[US] (UsOnly)
  • GRIFFIN, Graeme [GB]/[US] (UsOnly)
  • AMLER, Lukas, C. [DE]/[US] (UsOnly)
  • EBERHARD, David, A. [US]/[US] (UsOnly)
  • YAUCH, Robert, L. [US]/[US] (UsOnly)
Inventors
  • HALEY, John, D.
  • GRIFFIN, Graeme
  • AMLER, Lukas, C.
  • EBERHARD, David, A.
  • YAUCH, Robert, L.
Agents
  • STEWART, Alexander, A.
Priority Data
60/662,54516.03.2005US
60/671,82115.04.2005US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) BIOLOGICAL MARKERS PREDICTIVE OF ANTI-CANCER RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITORS
(FR) BIOMARQUEURS PREDICTIFS DE REPONSE ANTICANCEREUSE A DES INHIBITEURS DE KINASE DE RECEPTEUR DE FACTEUR DE CROISSANCE EPIDERMIQUE
Abstract
(EN)
The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.
(FR)
L'invention concerne des méthodes de diagnostic et de prognostic permettant de prédire l'efficacité du traitement d'un patient souffrant d'un cancer à l'aide d'un inhibiteur de kinase de récepteur de facteur de croissance épidermique (EGFR). Lesdites méthodes qui permettent de prédire la sensibilité d'un facteur de croissance tumorale à une inhibition à l'aide d'un inhibiteur de kinase EGFR, consistent à évaluer si la cellule tumorale a subi une transition épithéliale vers une transition mésenchymale (EMT) par détermination du niveau d'expression de biomarqueurs épithéliaux et/ou mésenchymaux, les cellules tumorales ayant subi une EMT étant sensiblement moins sensibles à une inhibition au moyen d'un inhibiteur de kinase EGFR. L'invention concerne également des méthodes améliorées permettant de traiter des patients souffrant d'un cancer au moyen d'inhibiteurs de kinase EGFR qui incorporent la méthodologie précitée. L'invention concerne en outre des méthodes permettant d'identifier de nouveaux biomarqueurs prédictifs de la réceptivité des tumeurs à des inhibiteurs de kinase EGFR. L'invention concerne enfin des méthodes permettant d'identifier des agents qui restaurent la sensibilité des cellules tumorales ayant subi une EMT à une inhibition au moyen d'inhibiteurs de kinase EGFR.
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