Compositions and methods of treating tumors

Abstract

Methods of treating an individual who has an erbB protein mediated tumor is disclosed. Methods of preventing erbB protein mediated tumors in an individual are disclosed. The methods comprise administering to the individual a nucleic acid molecule that encodes a protein that dimerizes with an erbB protein and that is deficient in tyrosine kinase activity. Composition that comprise such nucleic acid molecules including pharmaceutical compositions are disclosed.

1 - 45 . (canceled) 
     
     
         46 . A method of treating an individual who has an erbB-protein mediated tumor which method comprises the steps of:
 (a) administering to the individual an antibody or a peptide that disrupts tyrosine kinase activity associated with multimeric receptor ensembles in a tumor cell of the erbB-protein mediated tumor,   wherein said tumor is characterized by tumor cells that have multimeric receptor ensembles comprising an erbB protein which provides tyrosine kinase activity associated with a transformed phenotype,   said multimeric receptor ensembles being erbB heterodimers which are p185/EGFR heterodimers, p185/mutant EGFR heterodimers, p185/erbB3 heterodimers or p185/erbB4 heterodimers,   wherein disruption of said kinase activity has a cytostatic effect on the tumor cells and sensitizes the cells to radiation; and   (b) thereafter exposing the individual to a therapeutically effective amount of anti-cancer radiation.   
     
     
         47 . The method of  claim 46 , wherein the antibody or the peptide interacts with said multimeric receptor ensembles in the tumor cell so as to result in a decreased propensity to form such multimeric receptor ensemble. 
     
     
         48 . The method of  claim 46 , wherein the antibody or the peptide inhibits ligand-independent formation of erbB protein heterodimers. 
     
     
         49 . The method of  claim 46 , wherein the antibody or the peptide competitively inhibits formation of erbB protein heterodimers and prevents elevated tyrosine kinase activity. 
     
     
         50 . The method of  claim 46 , wherein the antibody or the peptide interacts with a monomeric component of the multimeric receptor ensembles and inhibits heterodimer formation between the monomeric components. 
     
     
         51 . The method of  claim 46 , wherein the antibody or the peptide inhibits the formation of p185/EGFR heterodimers. 
     
     
         52 . The method of  claim 46 , wherein the tumor cell is a p53(+) tumor cell. 
     
     
         53 . The method of  claim 46 , wherein the tumor cell is a p53(−) tumor cell. 
     
     
         54 . A method of treating an individual who has an erbB-protein mediated tumor which method comprises the steps of: (a) administering to the individual an agent that disrupts tyrosine kinase activity in a tumor cell of the erbB-protein mediated tumor, wherein the agent is not an antibody; and (b) thereafter exposing the individual to a therapeutically effective amount of anti-cancer radiation therapy or an anti-cancer chemotherapy, so as to thereby treat the individual with the erbB-protein mediated tumor. 
     
     
         55 . The method of  claim 54 , wherein the disrupted tyrosine kinase activity has a cytostatic effect on the tumor cell. 
     
     
         56 . The method of  claim 54 , wherein the erbB-protein mediated tumor is a p185-mediated tumor or an EGFR-mediated tumor. 
     
     
         57 . The method of  claim 54 , wherein the erbB-protein comprises a p185, mutant p185, EGFR, or a mutant EGFR protein. 
     
     
         58 . The method of  claim 54 , wherein the agent interacts with said erbB protein in a tumor cell to alter said erbB protein sufficiently to result in a decreased propensity of said erbB protein to dimerize with another erbB protein. 
     
     
         59 . The method of  claim 54 , wherein the agent inhibits ligand-independent formation of erbB protein dimers. 
     
     
         60 . The method of  claim 54 , wherein the agent competitively inhibits formation of erbB protein dimers and prevents elevated tyrosine kinase activity. 
     
     
         61 . A method of treating an individual who has an erbB-protein mediated tumor which method comprises the steps of:
 (a) administering to the individual a non-proteinaceous agent that disrupts tyrosine kinase activity associated with multimeric receptor ensembles in a tumor cell of the erbB-protein mediated tumor,   wherein said tumor is characterized by tumor cells that have multimeric receptor ensembles comprising an erbB protein which provides tyrosine kinase activity associated with a transformed phenotype,   said multimeric receptor ensembles being erbB heterodimers which are p185/EGFR heterodimers, p185/mutant EGFR heterodimers, p185/erbB3 heterodimers or p185/erbB4 heterodimers,   wherein disruption of said kinase activity has a cytostatic effect on the tumor cells and sensitizes the cells to radiation; and   (b) thereafter exposing the individual to a therapeutically effective amount of anti-cancer radiation.   
     
     
         62 . The method of  claim 61 , wherein the non-proteinaceous agent interacts with said multimeric receptor ensembles in the tumor cell so as to result in a decreased propensity to form said multimeric receptor ensemble. 
     
     
         63 . The method of  claim 61 , wherein the non-proteinaceous agent inhibits ligand-independent formation of erbB protein heterodimers. 
     
     
         64 . The method of  claim 61 , wherein the non-proteinaceous agent competitively inhibits formation of erbB protein heterodimers and prevents elevated tyrosine kinase activity. 
     
     
         65 . The method of  claim 61 , wherein the non-proteinaceous agent interacts with a monomeric component of the multimeric receptor ensembles and inhibits heterodimer formation between the monomeric components. 
     
     
         66 . The method of  claim 61 , wherein the non-proteinaceous agent inhibits the formation of p185/EGFR heterodimers. 
     
     
         67 . The method of  claim 61 , wherein the tumor cell is a p53(+) tumor cell. 
     
     
         68 . The method of  claim 61 , wherein the tumor cell is a p53(−) tumor cell.