Compositions and methods for treating neoplastic disease using chemotherapy and radiation sensitizers

Abstract

Inhibitors of KIAA0175 are provided that reduce the expression or biological activities of KIAA0175, p53 and/or p21 in a mammalian cell. KIAA0175 inhibitors include anti-sense molecules, ribozymes, antibodies and antibody fragments, proteins and polypeptides as well as small molecules. KIAA0175 inhibitors find use in compositions and methods for decreasing KIAA0175, p53 and/or p21 gene expression as well as methods for increasing the chemo and/or radiosensitivity of mammalian cells, including tumor cells, methods for decreasing the side effects of cancer therapy and methods for treating neoplastic diseases.

1 - 26 . (canceled)  
     
     
         27 . A method of treating neoplastic disease in a mammal in need of said treatment, comprising administering to said mammal a KIAA0175 inhibitor is selected from the group consisting of an anti-sense molecule, a ribozyme, an antibody, an antibody fragment, a protein, a polypeptide and a small molecule such that said neoplastic disease is reduced in severity.  
     
     
         28 . The method of  claim 27  wherein said KIAA0175 inhibitor is an anti-sense molecule.  
     
     
         29 . The method of  claim 27  wherein said anti-sense molecule or the complement thereof comprises at least 17 consecutive nucleic acids of the sequence of SEQ ID NO:9.  
     
     
         30 . The method of  claim 27  wherein said anti-sense molecule or the complement thereof hybridizes under high stringency conditions to the sequence of SEQ ID NO:9.  
     
     
         31 . The method of  claim 27  wherein said anti-sense molecule comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5.  
     
     
         32 . The method of  claim 27 , wherein said treating comprises increasing the chemosensitivity and/or radiosensitivity of a mammalian cell, wherein said mammalian cell is a tumorigenic cell.  
     
     
         33 . The method of  claim 32  wherein said increase in chemosensitivity and/or radiosensitivity is determined by a measurement selected from the group consisting of measuring a reduction in γ-irradiation or hydroxyurea induced p53 or p21 protein levels, measuring a reduction in γ-irradiation or hydroxyurea induced cell cycle arrest and measuring an increase in γ-irradiation or hydroxyurea induced cell sensitization.