G - Physics – 01 – N
Patent
G - Physics
01
N
G01N 33/50 (2006.01) G01N 33/574 (2006.01)
Patent
CA 2694356
The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R 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 IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R 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 IGF-1R kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-1R kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.
L'invention concerne des méthodes de diagnostic et de pronostic permettant de prévoir l'efficacité du traitement d'un patient atteint de cancer à l'aide d'un inhibiteur de la kinase de l'IGF-1R. L'invention concerne des méthodes destinées à prévoir la sensibilité de la croissance des cellules tumorales à l'inhibition par un inhibiteur de la kinase de l'IGF-1R, consistant à évaluer si la cellule tumorale a subi une transformation épithéliale-mésenchymale (EMT) par détermination du niveau d'expression des biomarqueurs épithéliaux et/ou mésenchymaux, les cellules tumorales ayant subi une EMT étant sensiblement moins sensibles à l'inhibition par les inhibiteurs de la kinase de l'IGF-1R. L'invention concerne également des méthodes améliorées incorporant ladite méthodologie. L'invention concerne, de plus, des méthodes d'identification de nouveaux biomarqueurs de prédiction de la réponse des tumeurs aux inhibiteurs de la kinase de l'IGF-1R. L'invention concerne en outre des méthodes d'identification d'agents destinés à restaurer la sensibilité des cellules tumorales ayant subi une EMT à l'inhibition par des inhibiteurs de la kinase de l'IGF-1R. L'invention concerne enfin pErk, HER3 et pHER, des biomarqueurs efficaces de prédiction de la sensibilité des cellules tumorales aux inhibiteurs de la kinase de l'IGF-1R.
Buck Elizabeth A.
Haley John D.
Cassan Maclean
Osi Pharmaceuticals Inc.
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