Methods for treating neuroblastoma

Abstract

The present invention provides methods and kits a) for preventing and/or treating neuroblastoma (e.g., high-risk neuroblastoma) that is linked, in part, to high levels of ODC activity and increased cellular polyamine content, b) for predicting cancer patient survival, especially cancer patients whose cancer is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and c) for selecting treatment options for such patients based on the allelic nucleotide sequence or SNP at positions +263 and/or +316 of the ODC1 gene. The invention also provides, cancer treatment methods comprising the determination of the ODC1 genotype at the +263 and/or +316 positions, as a means to guide treatment selection, which includes, in some aspects the administration of pharmaceutically effective amounts of α-difluoromethylomithine (DFMO), either as a monotherapy or in combination with one or more other drugs. In addition, the present invention provides methods for preventing and/or treating patients that have been determined to have cancer stem cells, such as patients in cancer remission that are at risk for relapse.

1 - 14 . (canceled) 
     
     
         15 . A method for the preventative or curative treatment of neuroblastoma in a patient comprising:
 a) obtaining results from a test that determines the patient's genotype at rs2302616 (position +263) of at least one ODC1 allele; and   b) if the results indicate that the patient's genotype at rs2302616 of at least one allele of the ODC1 gene is T, administering to the patient an effective amount of a pharmaceutical therapy comprising α-difluoromethylornithine (DFMO).   
     
     
         16 - 55 . (canceled) 
     
     
         56 . The method of  claim 15 , further defined as a method for preventing the development or recurrence of a neuroblastoma in a patient at risk therefor. 
     
     
         57 - 80 . (canceled) 
     
     
         81 . A method for preventing the development or recurrence of a carcinoma in a patient at risk thereof comprising:
 a) obtaining results from a test that determines the presence of cancer stem cells in a sample from the patient; and   b) administering to the patient an effective amount of α-difluoromethylornithine (DFMO) if the results indicate that the patient's sample comprises cancer stem cells.   
     
     
         82 - 107 . (canceled) 
     
     
         108 . A method for the preventative or curative treatment of neuroblastoma in a patient comprising administering to the patient effective amounts of a pharmaceutical therapy comprising an anti-GD2 therapy and a first agent that inhibits ornithine decarboxylase (ODC) within the patient. 
     
     
         109 . The method of  claim 108 , wherein the anti-GD2 therapy is a GD2 antibody or a GD2 vaccine. 
     
     
         110 . The method of  claim 108 , wherein the method reduces the risk of allodynia within the patient compared with a method that administers to the patient an effective amount of a pharmaceutical therapy comprising an anti-GD2 therapy without an agent that inhibits ornithine decarboxylase (ODC) within the patient. 
     
     
         111 . The method of  claim 108 , wherein the first agent that inhibits ornithine decarboxylase (ODC) within the patient is alpha-difluoromethylornithine (DFMO). 
     
     
         112 . The method of  claim 111 , further comprising administering a second agent that modulates the polyamine pathway to reduce overall polyamine content within the patient when combined with the agent that inhibits ornithine decarboxylase (ODC) within the patient. 
     
     
         113 . The method of  claim 111 , wherein the second agent that modulates the polyamine pathway to reduce overall polyamine content within the patient is a non-steroidal anti-inflammatory drug (NSAID). 
     
     
         114 . The method of  claim 113 , wherein the NSAID is aspirin, sulindac, or celecoxib. 
     
     
         115 . The method of  claim 108 , further comprising obtaining results from a test that determines that patient's genotype at rs2302615 (position +3161 of at least one ODC1 allele promoter and administering to the patient effective amounts of the pharmaceutical therapy if the results indicate that the patient's genotype at rs2302615 of at least one ODC1 allele promoter is G. 
     
     
         116 - 118 . (canceled) 
     
     
         119 . The method of  claim 115 , wherein the test determines the nucleotide bases at rs2302615 of both alleles of the ODC1 promoter of the patient. 
     
     
         120 . The method of  claim 119 , wherein the results indicate that the patient's genotype at rs2302615 of both alleles of the ODC1 promoter is GG. 
     
     
         121 . The method of  claim 119 , wherein the results indicate that the patient's genotype at rs2302615 of both alleles of the ODC1 promoter is GA. 
     
     
         122 . The method of  claim 108 , further comprising obtaining results from a test that determines that the patient's genotype at rs2302616 (position +263) of at least one ODC1 allele promoter and administering to the patient effective amounts of the pharmaceutical therapy if the results indicate that the patient's genotype at rs2302616 of at least one ODC1 allele promoter is T. 
     
     
         123 - 125 . (canceled) 
     
     
         126 . The method of  claim 122 , wherein the test determines the nucleotide bases at rs2302616 of both alleles of the ODC1 promoter of the patient. 
     
     
         127 . The method of  claim 126 , wherein the results indicate that the patient's genotype at rs2302616 of both alleles of the ODC1 promoter is TT. 
     
     
         128 . The method of  claim 126 , wherein the results indicate that the patient's genotype at rs2302616 of both alleles of the ODC1 promoter is TG. 
     
     
         129 - 132 . (canceled) 
     
     
         133 . The method of  claim 111 , wherein DFMO is administered orally. 
     
     
         134 - 135 . (canceled) 
     
     
         136 . The method of  claim 133 , wherein DFMO is formulated for pediatric administration. 
     
     
         137 - 149 . (canceled)