THYMIDYLATE SYNTHASE POLYMORPHISM FOR PREDICTING CHEMOTHERAPEUTIC RESPONSE

摘要

The present invention relates to the use of genomic polymorphism to provideindividualized therapeutic regimens to treat patients suffering from diseasessuch as cancer. The invention discloses methods for determining the efficacyor choice of chemotherapeutic drugs and regimens for use in treating adiseased patient by associating genomic polymorphism with the effectiveness ofthe drugs or regimens, or by associating genomic polymorphism with theintratumoral expression of a gene whereby the gene expression affectseffectiveness of the drugs or regimens. In particular, the present inventionprovides novel methods for screening therapeutic regimens, which comprisedetermining a patient's genotype at a tandemly repeated 28 base pair region inthe thymidilate synthase (TS) gene's 5' untranslated region (UTR). Patientshomozygous for a triple repeat will least successfully treated with athymidylate synthase directed drug, while those heterozygous for a triple anda double repeat will be more successfully treated, and those homozygous for adouble repeat will be even more successfully treated. Those patientshomozygous for the double repeat will likely suffer the least side effectsfrom thymidylate synthase directed drugs such as 5-FU.