Akt phosphorylation at ser473 as an indicator for taxane-based chemotherapy

Abstract

Methods for determining whether a cancer patient is likely to benefit from treatment with a taxane compound based on Akt-Ser473 phosphorylation status are provided, together with kits for determining Akt-Ser473 phosphorylation status and methods for improving treatment of a cancer patient that include obtaining a determination of the Akt-Ser473 phosphorylation status of the cancer.

What is claimed: 
     
         1 . A method of treating cancer in a patient, comprising determining the phosphorylation status of Akt, and if the phosphorylation status of Akt is determined to be positive, treating with a therapeutically effective amount of a taxane compound, wherein said treatment with a taxane compound is provided as treatment for advanced or metastatic cancer. 
     
     
         2 . The method of  claim 1 , wherein said cancer is breast cancer. 
     
     
         3 . The method of  claim 1 , wherein the phosphorylation status is determined by conducting at least one immunohistochemistry assay of a tumor tissue sample before therapy so as to obtain physical data regarding the expression status of phosphorylated Akt-Ser473 (pAkt) protein in the sample. 
     
     
         4 . The method of  claim 3  wherein said determination comprises incubating an antibody specific for pAkt with a sample from said cancer and detecting the presence of bound pAkt-specific antibody. 
     
     
         5 . The method of  claim 4 , wherein the antibody specifically binds to a phosphorylated peptide consisting of the Akt sequence SERRPHFPQF {pSerine473}YSA-NH2. 
     
     
         6 . The method of  claim 1 , wherein said taxane compound comprises docetaxel or paclitaxel. 
     
     
         7 . The method of  claim 6 , wherein the cancer is selected from the group consisting of breast, colorectal, lung, ovarian, liver, renal, head and neck, prostate, and stomach. 
     
     
         8 . The method of  claim 1 , wherein said taxane compound is paclitaxel. 
     
     
         9 . The method of  claim 8 , wherein the cancer is breast cancer. 
     
     
         10 . A method for identifying a metastatic cancer patient that is likely to respond to or benefit from taxane therapy, comprising determining the phosphorylation status of Akt, wherein the patient will benefit from treatment with a therapeutically effective amount of a taxane compound if the phosphorylation status of Akt is positive. 
     
     
         11 . The method of  claim 10 , wherein the response is tumor reduction during or after taxane therapy. 
     
     
         12 . The method of  claim 10 , wherein the benefit is longer progression-free survival or overall survival. 
     
     
         13 . The method of  claim 10 , wherein the cancer is breast cancer. 
     
     
         14 . The method of  claim 13 , wherein the taxane therapy comprises treatment with taxane chemotherapy in HER2-negative breast cancer 
     
     
         15 . The method of  claim 13 , wherein the taxane therapy comprises treatment with taxane in combination with anti-HER2 therapy in HER2-positive breast cancer. 
     
     
         16 . The method of  claim 10 , wherein the phosphorylation status is determined by incubating an antibody specific for pAkt with a sample from said cancer and detecting the presence of bound pAkt-specific antibody. 
     
     
         17 . The method of  claim 16 , wherein the antibody specifically binds to a phosphorylated peptide consisting of the Akt sequence SERRPHFPQF {pSerine473}YSA-NH2. 
     
     
         18 . A method for identifying a metastatic cancer patient that is not amenable to taxane therapy, comprising determining the phosphorylation status of Akt before therapy, wherein the patient will be amenable to treatment with taxane compound if the phosphorylation status of Akt is negative due to less responsiveness to taxane chemotherapy or shorter progression-free survival or shorter overall survival. 
     
     
         19 . The method of  claim 18 , wherein the cancer is selected from the group consisting of breast, colorectal, lung, ovarian, liver, renal, head and neck, prostate, and stomach.