Capcna peptide therapeutics for cancer

Abstract

Administration of compositions comprising cell-permeable cancer-specific proliferating cell nuclear antigen derived peptides and their variants reduces the proliferation of cancer cells and also augments cytotoxic effects of chemotherapeutics. The compositions are effective in cells harboring mutations in DNA repair proteins.

1 - 17 . (canceled) 
     
     
         18 . A method of reducing the effective dose of a chemotherapeutic agent required to treat cancer, the method comprising administering a caPCNA peptide and a chemotherapeutic agent to an individual diagnosed with a cancer associated with one or more mutations in a DNA repair protein. 
     
     
         19 . The method of  claim 18 , wherein the effective dose of the chemotherapeutic agent is from about 25% to about 75% less than the standard chemotherapeutic dose for the agent. 
     
     
         20 . The method according to  claim 18  wherein the cancer is breast cancer. 
     
     
         21 . The method according to  claim 18  wherein the cancer is ovarian cancer. 
     
     
         22 . The method according to  claim 18  wherein the cancer is prostate cancer. 
     
     
         23 . A method of inducing cell death in a cancer cell or a pre-malignant cell, the method comprising administering a therapeutically effective amount of a composition comprising a caPCNA peptide molecule, wherein the caPCNA peptide comprises an amino acid sequence selected from LGIPEQEY (SEQ ID NO: 1), LAIPEQEY (SEQ ID NO: 2), LGIAEQEY (SEQ ID NO: 3), LGIPAQEY (SEQ ID NO: 4), LGIPEAEY (SEQ ID NO: 5), LGIPEQAY (SEQ ID NO: 6), LGIAEAEY (SEQ ID NO: 7), LGIPEAAY (SEQ ID NO: 8), LGIAEQAY (SEQ ID NO: 9), and LGIAEAAY (SEQ ID NO: 10), wherein the cell has a mutation in a DNA repair protein. 
     
     
         24 . A method of inducing cell death in a cancer cell or a pre-malignant cell containing a BRCA1 mutation, the method comprising administering a therapeutically effective amount of a composition comprising a caPCNA peptide molecule, wherein the caPCNA peptide molecule comprises an amino acid sequence selected from LGIPEQEY (SEQ ID NO: 1), LAIPEQEY (SEQ ID NO: 2), LGIAEQEY (SEQ ID NO: 3), LGIPAQEY (SEQ ID NO: 4), LGIPEAEY (SEQ ID NO: 5), LGIPEQAY (SEQ ID NO: 6), LGIAEAEY (SEQ ID NO: 7), LGIPEAAY (SEQ ID NO: 8), LGIAEQAY (SEQ ID NO: 9), and LGIAEAAY (SEQ ID NO: 10), and cisplatin. 
     
     
         25 . The method according to  claim 24 , wherein the caPCNA peptide molecule further comprises a cell penetrating peptide sequence selected from RRRRRRR (SEQ ID NO: 11), RRRRRRRR (SEQ ID NO: 12), RRRRRRRRR (SEQ ID NO: 13), RRRRRRRRRR (SEQ ID NO: 14), RRRRRRRRRRR (SEQ ID NO: 15), RQIKIWFQNRRMKWKK (SEQ ID NO: 16), GRKKRRQRRRPPQ (SEQ ID NO: 17), GWTLNSAGYLLGKINLKALAALAKKIL (SEQ ID NO: 18), and GRKKRRQRRR (SEQ ID NO: 19).