Biological Markers Predictive of Anti-Cancer Response to Insulin-Like Growth Factor-1 Receptor Kinase Inhibitors

Abstract

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, pErk, HER 3 and pHER are also demonstrated to be effective biomarkers for predicting sensitivity of tumor cells to IGF-1R kinase inhibitors.

1 - 8 . (canceled) 
     
     
         9 . A method for treating pancreatic tumors or tumor metastases in a patient, comprising:
 diagnosing that a patient is likely to be responsive to an IGF-1R kinase inhibitor by assessing that pancreatic tumor cells of the patient have not undergone an epithelial-mesenchymal transition; and   administering to said patient a therapeutically effective amount of an IGF-1R kinase inhibitor;   wherein diagnosing that a patient is likely to be responsive to an IGF-1R kinase inhibitor is determined by assessing that the level of the mesenchymal biomarker SNAI1 is not high in pancreatic tumor cells from the patient, relative to the expression level of SNAI1 in non-tumor cells of the same tissue.   
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 9 , wherein one or more additional anti-cancer agents are co-administered simultaneously or sequentially with the IGF-1R kinase inhibitor. 
     
     
         12 - 31 . (canceled) 
     
     
         32 . The method of  claim 9 , wherein the IGF-1R kinase inhibitor administered is cis-3-[8-amino-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol (OSI-906). 
     
     
         33 - 34 . (canceled) 
     
     
         35 . A method for treating pancreatic tumors or tumor metastases in a patient, comprising administering to said patient a therapeutically effective amount of an IGF-1R kinase inhibitor if the level of the mesenchymal biomarker SNAI1 is not high in pancreatic tumor cells from the patient, relative to the expression level of SNAI1 in non-tumor cells of the same tissue, indicating the patient's is likely to be responsive to an IGF-1R kinase inhibitor. 
     
     
         36 . The method of  claim 35 , wherein one or more additional anti-cancer agents are co-administered simultaneously or sequentially with the IGF-1R kinase inhibitor. 
     
     
         37 . The method of  claim 35 , wherein the IGF-1R kinase inhibitor administered is cis-3-[8-amino-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-1-methyl-cyclobutanol (OSI-906).