G - Physics – 01 – N
Patent
G - Physics
01
N
G01N 33/574 (2006.01)
Patent
CA 2694154
The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-IR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-IR 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-IR kinase inhibitors. Improved methods for treating cancer patients with IGF-IR 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-IR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by IGF-IR kinase inhibitors are also provided. pErk, HER3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF- IR kinase inhibitors.
L'invention concerne des procédés de diagnostic et de pronostic qui permettent de prédire l'efficacité d'un traitement par un inhibiteur de kinase IGF-1R chez un patient souffrant d'un cancer. Les procédés de l'invention permettent de prédire la sensibilité de la croissance d'une cellule tumorale à l'inhibition par un inhibiteur de kinase IGF-1R, lesquels procédés consistent à évaluer si la cellule tumorale a subi une transition épithélio-mésenchymateuse (TEM) en mesurant le niveau d'expression de biomarqueurs épithéliaux et/ou mésenchymateux, les cellules tumorales qui ont subi une transition TEM étant notablement moins sensibles à l'inhibition par les inhibiteurs de kinase IGF-1R. L'invention se rapporte à des procédés améliorés qui permettent de traiter des patients atteints de cancer par des inhibiteurs de kinase IGF-1R selon la méthodologie précitée. L'invention concerne en outre des procédés qui permettent d'identifier de nouveaux biomarqueurs prédictifs d'une réponse tumorale aux inhibiteurs de kinase IGF-1R. L'invention se rapporte aussi à des procédés d'identification d'agents destinés à renforcer la sensibilité des cellules tumorales ayant subi une transition TEM à l'inhibition par des inhibiteurs de kinase IGF-1R. Il a aussi été démontré que pErk, HER3 et pHER sont des biomarqueurs efficaces qui permettent de prédire la sensibilité des cellules tumorales aux inhibiteurs de kinase IGF-1R.
Cassan Maclean
Osi Pharmaceuticals Inc.
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