Cancer Therapy

Abstract

The present invention provides a method for treating a hyperproliferative disorder characterized by expression of a mutant form of p53 in a subject, the method comprising administering to the subject a therapeutically effective amount of an agent which inhibits promyelocytic leukemia (PML) protein.

What is claimed is: 
     
         1 . A method for treating a cancer characterized by expression of a mutant form of p53 in a subject, the method comprising administering to the subject a therapeutically effective amount of an agent which inhibits promyelocytic leukemia (PML) protein, wherein said mutant form of p53 comprises a mutation selected from the group consisting of R175H, R273H and P309S. 
     
     
         2 . A method for inhibiting one or both of the survival and proliferation of tumor cells expressing a mutant form of p53, the method comprising exposing the tumor cells to an effective amount of an agent which inhibits promyelocytic leukemia (PML) protein, wherein said mutant form of p53 comprises a mutation selected from the group consisting of R175H, R273H and P309S. 
     
     
         3 . The method of  claim 1 , wherein the agent inhibits the transcription of a gene encoding PML protein. 
     
     
         4 . The method of  claim 1 , wherein the agent is selected from the group consisting of a shRNA, siRNA, miRNA, DNAzyme, ribozyme, antisense and morpholino or other iRNA molecule targeted against PML mRNA. 
     
     
         5 . The method of  claim 1 , wherein the cancer is selected from the group consisting of ovarian cancer, colorectal cancer, esophageal cancer, head and neck cancer, larynx cancer, skin cancer, pancreatic cancer, stomach cancer, liver cancer, brain cancer, bladder cancer, uterine cancer, prostate cancer, bone cancer, endocrine gland cancer, leukemia-hematological malignancy, lung cancer, breast cancer, cervical cancer and colon cancer. 
     
     
         6 . The method of  claim 2 , wherein the tumor cell is a tumor cell from a cancer selected from the group consisting of ovarian cancer, colorectal cancer, esophageal cancer, head and neck cancer, larynx cancer, skin cancer, pancreatic cancer, stomach cancer, liver cancer, brain cancer, bladder cancer, uterine cancer, prostate cancer, bone cancer, endocrine gland cancer, leukemia-hematological malignancy, lung cancer, breast cancer, cervical cancer and colon cancer. 
     
     
         7 . The method of  claim 4 , wherein the agent is a shRNA targeted against PML mRNA. 
     
     
         8 . The method of  claim 7 , wherein the shRNA is targeted against SEQ ID NO: 1. 
     
     
         9 . The method of  claim 7 , wherein the shRNA is targeted against SEQ ID NO: 2. 
     
     
         10 . The method according to  claim 4 , wherein the agent is a siRNA targeted against PML mRNA. 
     
     
         11 . The method of  claim 10 , wherein the siRNA is targeted against SEQ ID NO: 3. 
     
     
         12 . The method of  claim 2 , wherein the agent inhibits the transcription of a gene encoding PML protein. 
     
     
         13 . The method of  claim 2 , wherein the agent is selected from the group consisting of a shRNA, siRNA, miRNA, DNAzyme, ribozyme, antisense and morpholino or other iRNA molecule targeted against PML mRNA. 
     
     
         14 . The method of  claim 13 , wherein the agent is a shRNA targeted against PML mRNA. 
     
     
         15 . The method according to  claim 13 , wherein the agent is a siRNA targeted against PML mRNA.