Inhibition of stress activated protein kinase (sapk) pathway and sensitization of cells to cancer therapies

Abstract

The present invention provides compositions that can be administered to an individual and inhibit a stress activated protein kinase pathway. The invention also provides methods of increasing the sensitivity of cancer cells to a cancer therapy by contacting the cancer cells with a stress activated protein kinase pathway inhibitor. The invention further provides methods of reducing the severity of cancer in a patient by administering to the patients a stress activated protein kinase pathway inhibitor and treating the patient with a conventional cancer therapy.

What is claimed is:  
     
         1 . A method of increasing the sensitivity of cancer cells to a cancer therapy, comprising contacting the cancer cells with a stress activated protein kinase (SAPK) pathway inhibitor.  
     
     
         2 . The method of  claim 1 , wherein said SAPK pathway inhibitor is an antisense nucleic acid molecule.  
     
     
         3 . The method of  claim 2 , wherein said antisense nucleic acid molecule is an antisense SAPK nucleic acid molecule.  
     
     
         4 . The method of  claim 2 , wherein said SAPK nucleic acid molecule is selected from the group consisting of SAPK1α1, SAPK1α2, SAPK1β1, SAPK1β2, SAPK2α1, SAPK2β1, SAPK2β2, SAPK3α1 and SAPK3α2.  
     
     
         5 . The method of  claim 2 , wherein said antisense nucleic acid molecule is an antisense SAPK kinase kinase (MEKK1) nucleic acid molecule.  
     
     
         6 . The method of  claim 1 , wherein said SAPK pathway inhibitor is a ribozyme  
     
     
         7 . The method of  claim 1 , wherein said SAPK pathway inhibitor is a dominant negative mutant.  
     
     
         8 . The method of  claim 8 , wherein said dominant negative mutant is a dominant negative c-jun mutant.  
     
     
         9 . The method of  claim 8 , wherein said SAPK pathway inhibitor is a dominant negative SAPK mutant.  
     
     
         10 . The method of  claim 8 , wherein said SAPK pathway inhibitor is a dominant negative SAPK kinase kinase (MEKK1) mutant.  
     
     
         11 . A method of reducing the severity of a cancer in a patient, comprising administering to the patient a stress activated protein kinase pathway (SAPK) inhibitor and treating the patient with a cancer therapy.  
     
     
         12 . The method of  claim 11 , wherein said SAPK pathway inhibitor is an antisense nucleic acid molecule.  
     
     
         13 . The method of  claim 12 , wherein said antisense nucleic acid molecule is an antisense SAPK nucleic acid molecule.  
     
     
         14 . The method of  claim 12 , wherein said SAPK nucleic acid molecule is selected from the group consisting of SAPK1α1, SAPK1α2, SAPK1β1, SAPK1β2, SAPK2α1, SAPK2β1, SAPK2β2, SAPK3α1 and SAPK3α2.  
     
     
         15 . The method of  claim 12 , wherein said antisense nucleic acid molecule is an antisense SAPK kinase kinase (MEKK1) nucleic acid molecule.  
     
     
         16 . The method of  claim 11 , wherein said SAPK pathway inhibitor is a ribozyme.  
     
     
         17 . The method of  claim 11 , wherein said SAPK pathway inhibitor is a dominant negative mutant.  
     
     
         18 . The method of  claim 17 , wherein said dominant negative mutant is a dominant negative c-jun mutant.  
     
     
         19 . The method of  claim 17 , wherein said SAPK pathway inhibitor is a dominant negative SAPK mutant.  
     
     
         20 . The method of  claim 17 , wherein said SAPK pathway inhibitor is a dominant negative SAPK kinase kinase (MEKK1) mutant.  
     
     
         21 . A composition, comprising a stress activated protein kinase (SAPK) pathway inhibitor and a carrier acceptable for administration to an individual.  
     
     
         22 . The composition of  claim 21 , wherein said SAPK pathway inhibitor is an antisense nucleic acid molecule.  
     
     
         23 . The composition of  claim 22 , wherein said antisense nucleic acid molecule is an antisense SAPK nucleic acid molecule.  
     
     
         24 . The composition of  claim 22 , wherein said SAPK nucleic acid molecule is selected from the group SAPK2α1, SAPK2β1, SAPK2β2, SAPK3α1 and SAPK3α2.  
     
     
         25 . The composition of  claim 22 , wherein said antisense nucleic acid molecule is an antisense SAPK kinase kinase (MEKK1) nucleic acid molecule.  
     
     
         26 . The composition of  claim 21 , wherein said SAPK pathway inhibitor a ribozyme.  
     
     
         27 . The composition of  claim 21 , wherein said SAPK pathway inhibitor is a dominant negative mutant.  
     
     
         28 . The composition of  claim 27 , wherein said dominant negative mutant is a dominant negative c-jun mutant.  
     
     
         29 . The method of  claim 27 , wherein said SAPK pathway inhibitor is a dominant negative SAPK mutant.  
     
     
         30 . The method of  claim 27 , wherein said SAPK pathway inhibitor is a dominant negative SAPK kinase kinase (MEKK1) mutant.