Method

Abstract

The use of Akt3 as a biomarker for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject, and the use of Akt3 inhibitors to treat cancer is disclosed herein. Also disclosed are various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring Akt3 expression and/or activity.

1 .- 67 . (canceled) 
     
     
         68 . A method of diagnosing and treating cancer comprising: (a) obtaining a sample from a subject; (b) detecting a level of epithelial-to-mesenchymal transition (EMT) in the sample from the subject by contacting the sample with a reagent that specifically binds Akt3 protein or Akt3 mRNA and detecting the expression level of Akt3 in the sample; (c) diagnosing the subject with increased risk of cancer when the level of EMT is increased in the sample as compared to a reference level; and (d) administering an effective amount of a therapeutic agent or radiotherapeutic treatment to the subject diagnosed with increased risk of cancer. 
     
     
         69 . The method of  claim 68 , wherein the cancer is a cancer selected from the group consisting of: acute myeloid leukemia (AML), myelodysplatic syndrome (MDS), non-small-cell lung carcinoma (NSCLC), melanoma, triple negative breast cancer, ovarian cancer, glioma, bladder cancer, gastric cancer, hepatocellular carcinoma (HCC), and prostate cancer. 
     
     
         70 . The method of  claim 68 , wherein Akt3 mRNA is detected in step (b). 
     
     
         71 . The method of  claim 70 , wherein Akt3 mRNA comprises an mRNA encoding the protein of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         72 . The method of  claim 68 , wherein Akt3 protein is detected in step (b). 
     
     
         73 . The method of  claim 72 , wherein Akt3 protein comprises SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         74 . The method of  claim 68 , wherein the therapeutic agent comprises a chemotherapeutic agent. 
     
     
         75 . The method of  claim 68 , wherein the therapeutic agent comprises an Axl inhibitor and/or Akt3 inhibitor. 
     
     
         76 . The method of  claim 68 , wherein the therapeutic agent comprises BGB324/R428. 
     
     
         77 . A method of treating cancer in a subject comprising: contacting a sample from the subject with a reagent that specifically binds Akt3 protein or Akt3 mRNA; detecting the expression level of Akt3 to determine the level of epithelial-to-mesenchymal transition (EMT) as compared to a reference level; and administering a therapeutically effective amount of a therapeutic agent or radiotherapeutic treatment to the subject provided that a sample from the subject has an increased level of epithelial-to-mesenchymal transition (EMT) as compared to a reference level. 
     
     
         78 . The method of  claim 77 , wherein the cancer is a cancer selected from the group consisting of: acute myeloid leukemia (AML), myelodysplatic syndrome (MDS), non-small-cell lung carcinoma (NSCLC), melanoma, triple negative breast cancer, ovarian cancer, glioma, bladder cancer, gastric cancer, hepatocellular carcinoma (HCC), and prostate cancer. 
     
     
         79 . The method of  claim 77 , wherein Akt3 mRNA is contacted. 
     
     
         80 . The method of  claim 79 , wherein Akt3 mRNA comprises an mRNA encoding the protein of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         81 . The method of  claim 77 , wherein Akt3 protein is contacted. 
     
     
         82 . The method of  claim 81 , wherein Akt3 protein comprises SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         83 . The method of  claim 77 , wherein the therapeutic agent comprises a chemotherapeutic agent. 
     
     
         84 . The method of  claim 77 , wherein the therapeutic agent comprises an Axl inhibitor and/or Akt3 inhibitor. 
     
     
         85 . The method of  claim 77 , wherein the therapeutic agent comprises BGB324/R428. 
     
     
         86 . A cell line which is sensitive to inhibitors of epithelial-to-mesenchymal transition (EMT), the cell line having a level of Akt3 expression that is just insufficient to prevent EMT.