A sensitive diagnostic test to identify cancer patients that may experience 5-Fluorouracil toxicity has been developed by scientists at the National Cancer Institute (NCI).
5-Fluorouracil (5-FU) is used for the treatment of multiple cancers, including breast and colon cancers. In the United States, approximately 275,000 cancer patients receive 5-FU annually. Although most anti-cancer treatments are associated with some negative side effects, some patients treated with the anti-cancer drug 5-FU will have fatal reactions to the drug, typically caused by cardio-toxicity. It is estimated that 3% of the patients treated with 5-FU will develop some degree of toxic reaction and approximately 15% of those developing a toxic reaction will die as a result of receiving 5-FU. In the United States alone, more than 1,300 patients die each year as a result of 5-FU toxicity. These deaths are all potentially avoidable if patients are screened prior to the administration of 5-FU using the diagnostic test developed by NCI.
The diagnostic test is based upon screening for a mutation in the dihydropyrimidine dehydrogenase (DPD) gene. DPD is involved with the degradation of 5-FU, and it has been shown that patients exhibiting 5-FU toxicity have low DPD activity levels. In 1994, Dr. Frank Gonzalez and his colleague at the NCI determined the molecular basis (a splicing mutation) for the DPD deficiency observed in patients with 5-FU toxicity and developed a method to detect the mutation. Since that time, this discovery has been translated into multiple commercial products that are used to detect the mutation and allow health care providers to provide optimal anti-cancer treatment.
This technology has been licensed nonexclusively to several companies. The transfer of this technology through these nonexclusive licenses has enabled the wide dissemination of this test in the United States and Europe. As a result of these multiple licenses, many more people around the globe can forego being treated by a drug that may prove to do more harm than good in genetically predisposed individuals. The wide dissemination of this life-saving diagnostic test promotes the NIH mission of improving public health.
