Use of orotidine monophosphate decarboxylase inhibition in a met

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...

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436 63, 436 64, C12Q 100, G01N 3348

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active

061300357

ABSTRACT:
The present invention provides a method of screening for the presence or absence of cancer characterized by increased DNA synthesis. The present invention also provides a method of monitoring the effectiveness of treatment of cancer characterized by increased DNA synthesis. The methods are based on the observation that increased de novo pyrimidine biosynthesis is characteristic of malignant solid tumors. An initial step of pyrimidine biosynthesis is the conversion of orotidine monophosphate (OMP) to uridine monophosphate by OMP decarboxylase which is inhibited by mononucleotide precursors such as 6-hydroxyuridine, 6-azauridine, uridine, allopurinol and oxipurinol. Inhibition of OMP decarboxylase results in accumulation of orotidine and orotate which can be measured in a urine sample. The accumulation of oritidine and orotate, in amounts above that of a control, provides an indicator that the subject has a cancer characterized by having increased DNA synthesis.

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