Carcinoma diagnosis and treatment, based on odc1 genotype

Abstract

The present invention provides methods and kits a) for predicting colorectal cancer patient survival, as well as the survival of patients harboring other invasive cancers where cellular proliferation and carcinogenesis is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and b) for selecting the corresponding treatment options for such patients based on the allelic nucleotide sequence or SNP at position +316 of the ODC1 promoter gene as well as cancer treatment methods, in each case, which include the determination of the ODC1 promoter +316 position genotype, as a means to guide treatment selection.

1 - 121 . (canceled) 
     
     
         122 . A method for treating a patient with carcinoma, the method comprising administering to a patient with carcinoma a combination therapy comprising a combined effective amount of an ornithine decarboxylase (ODC) inhibitor and an agent that modulates the polyamine pathway to reduce overall cellular polyamine content, said patient having been determined to have a dietary polyamine intake that is 300 μmol polyamine per day or lower. 
     
     
         123 . The method of  claim 122 , wherein said patient has been further determined to have a G at rs2302615 (position +316) of at least one allele of the ODC1 gene promoter. 
     
     
         124 . The method of  claim 123 , wherein said patient has been further determined to have a genotype of GG at rs2302615 of both alleles of the ODC1 gene promoter. 
     
     
         125 . The method of  claim 123 , wherein said patient has been further determined to have a genotype of GA at rs2302615 of both alleles of the ODC1 gene promoter. 
     
     
         126 . The method of  claim 123 , wherein the method prevents ototoxicity or the risk thereof within the patient. 
     
     
         127 . The method of  claim 122 , wherein said ornithine decarboxylase (ODC) inhibitor is α-difluoromethylornithine (DFMO). 
     
     
         128 . The method of  claim 122 , wherein the agent that modulates the polyamine pathway to reduce overall cellular polyamine content is a spermidine/spermine N 1 -acetyltransferase expression agonist. 
     
     
         129 . The method of  claim 128 , wherein said spermidine/spermine N 1 -acetyltransferase expression agonist is a non-aspirin containing non-steroidal anti-inflammatory drug (NSAID). 
     
     
         130 . The method of  claim 129 , wherein said non-aspirin containing NSAID is a selective COX-2 inhibitor. 
     
     
         131 . The method of  claim 130 , wherein said non-aspirin containing NSAID is sulindac. 
     
     
         132 . The method of  claim 122 , wherein said dietary polyamine intake is determined from a patient dietary history. 
     
     
         133 . The method of  claim 122 , wherein said patient has a solid tumor, and said method further comprises resection of said solid tumor. 
     
     
         134 . The method of  claim 132 , wherein DFMO and sulindac are administered prior to said resection. 
     
     
         135 . The method of  claim 132 , wherein DFMO and sulindac are administered after said resection. 
     
     
         136 . The method of  claim 122 , wherein the carcinoma is colorectal cancer, breast cancer, pancreatic cancer, brain cancer, lung cancer, stomach cancer, a blood cancer, skin cancer, testicular cancer, prostate cancer, ovarian cancer, liver cancer or esophageal cancer, cervical cancer, head and neck cancer, non-melanoma skin cancer, neuroblastoma, or glioblastoma. 
     
     
         137 . The method of  claim 136 , wherein the carcinoma is colorectal cancer. 
     
     
         138 . The method of  claim 137 , wherein the colorectal cancer is associated with familial adenomatous polyposis. 
     
     
         139 . The method of  claim 122 , wherein the patient is a human. 
     
     
         140 . A method for preventing recurrence in a patient previously diagnosed with carcinoma, the method comprising administering to a patient previously diagnosed with carcinoma a combined effective amount of an ornithine decarboxylase (ODC) inhibitor and a spermidine/spermine N 1 -acetyltransferase expression agonist, said patient having been determined to have a dietary polyamine intake that is 300 μmol polyamine per day or lower. 
     
     
         141 . A method for preventing carcinoma in a patient having a familial history of carcinoma, the method comprising administering to a patient having a familial history of carcinoma a combined effective amount of an ornithine decarboxylase (ODC) inhibitor and a spermidine/spermine N 1 -acetyltransferase expression agonist, said patient having been determined to have a dietary polyamine intake that is 300 μmol polyamine per day or lower.