Thymidylate synthase gene amplification in a colon tumor resistant to fluoropyrimidine chemotherapy.
We have identified amplification of the thymidylate synthase gene in a colonic tumor that had developed resistance to 5-fluorouracil/leucovorin combination chemotherapy. The tumor had previously undergone a partial response to this combination but began to progress following a prolonged period of continuous therapy and relative disease stabilization. Since thymidylate synthase is a target enzyme for 5-fluorouracil, it is likely that the observed gene amplification is responsible for the resistance. Thus, gene amplification may be a relevant mechanism of acquired resistance to fluoropyrimidine chemotherapy in the clinic.
D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance; D005472:Fluorouracil / Q000627:therapeutic use*; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D012004:Rectal Neoplasms / Q000235:genetics; D012086:Reoperation; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*
D004273:DNA, Neoplasm; D013940:Thymidylate Synthase; D005472:Fluorouracil