Method of Treating Colorectal Cancers Using a PKC Inhibitor

Abstract

The subject invention pertains to methods of treating colorectal cancer by administering an atypical PKC inhibitor. The inhibitors of aPKC useful in the methods of the instant invention include ACPD, ICA-1, DNDA and ζ-Stat. Also provided are methods of measuring the susceptibility of colon cancer cells of a subject to inhibitors of aPKCs.

1 - 6 . (canceled) 
     
     
         7 . A method of measuring the susceptibility of colon cancer cells of a subject suffering from colon cancer to an aPKC inhibitor, the method comprising:
 obtaining a colon cancer cell sample from a subject suffering from colon cancer, wherein the colon cell sample comprises colon cancer cells;   exposing a portion of the colon cancer cells of the colon cell sample to an inhibitor of an aPKC, while leaving another portion of the colon cancer cells of the colon cell sample untreated;   detecting cell proliferation, expression, and activation of one or more aPKCs in treated and untreated cells;   selecting a subject having a cancer susceptible to an aPKC inhibitor by detecting (i) the reduction of proliferation, expression and activation of one or more aPKCs in treated cells compared to untreated cells, wherein reduction indicates the subject's cancer is susceptible to aPKC inhibitors.   
     
     
         8 . The method, according to  claim 7 , wherein the one or more aPKC comprises PKC-τ. 
     
     
         9 . The method, according to  claim 7 , wherein the one or more aPKC comprises PKC-ζ. 
     
     
         10 . The method, according to  claim 7 , wherein the activation of one or more aPKC is detected as increased phosphorylation of the aPKC. 
     
     
         11 . The method, according to  claim 10 , wherein the increased phosphorylation is increased phosphorylation of PKC-τ. 
     
     
         12 . The method, according to  claim 10 , wherein the increased phosphorylation is increased phosphorylation of PKC-ζ. 
     
     
         13 . The method, according to  claim 7 , wherein the marker of apoptosis is Caspase-3. 
     
     
         14 . The method, according to  claim 7 , wherein the marker of anti-apoptosis is BCL-XL. 
     
     
         15 . The method, according to  claim 7 , wherein the marker of anti-apoptosis is survivin. 
     
     
         16 - 19 . (canceled) 
     
     
         20 . The method of  claim 7 , wherein when the subject's cancer is susceptible to aPKC inhibitors, further comprising:
 administering to the subject a therapeutically effective amount of an atypical PKC (aPKC) inhibitor selected from the group consisting of ACPD, ICA-1, DNDA, and ζ-Stat.   
     
     
         21 . The method of  claim 20 , wherein the aPKC inhibitor is ζ-Stat. 
     
     
         22 . The method of  claim 7 , wherein when the subject's cancer is not susceptible to aPKC inhibitors, further treating the subject with surgery, radiation therapy, or immunotherapy.