Ornithine Decarboxylase - Clinical Significance

Clinical Significance

ODC is a transcriptional target of the oncogene Myc and is upregulated in a wide variety of cancers. The polyamine products of the pathway initialized by ODC are associated with increased cell growth and reduced apoptosis. Ultraviolet light, asbestos and androgens released by the prostate gland are all known to induce increased ODC activity associated with cancer. Inhibitors of ODC such as eflornithine have been shown to effectively reduce cancers in animal models, and drugs targeting ODC are being tested for potential clinical use. The mechanism by which ODC promotes carcinogenesis is complex and not entirely known. Along with their direct effect on DNA stability, polyamines also upregulate gap junction genes and downregulate tight junction genes. Gap junction genes are involved in communication between carcinogenic cells and tight junction genes act as tumor suppressors.

ODC gene expression is induced by a large number of biological stimuli including seizure activity in the brain. Inactivation of ODC by difluoromethylornithine (eflornithine) is used to treat cancer and facial hair growth in postmenopausal females.

ODC is also an enzyme indispensable to parasites like trypanosoma, giardia, and plasmodium, a fact exploited by the drug eflornithine.