Biological markers predictive of anti-cancer response to...

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G01N 33/574 (2006.01) C12Q 1/48 (2006.01) G01N 33/74 (2006.01)

Patent

CA 2601157

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.

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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