Thymidylate synthase and drug resistance.
Eur J Cancer
; 31A(7-8): 1299-305, 1995.
Article
en En
| MEDLINE
| ID: mdl-7577040
ABSTRACT
Thymidylate synthase is an important target for both fluorinated pyrimidines and for new folate analogues. Resistance to 5-fluorouracil (5FU) can be related to insufficient inhibition of thymidylate synthase. The 5FU-nucleotide FdUMP induces inhibition of thymidylate synthase which is enhanced and retained for longer in the presence of increased folate pools, for which leucovorin is a precursor. In a murine model system, 5FU treatment caused a 4-fold induction of thymidylate synthase levels which may have contributed to resistance. Addition of leucovorin to this treatment prevented this induction and increased the antitumour effect 2-3-fold. In the clinical setting, 5FU administration to patients resulted in approximately 50% inhibition of TS after 48 h. The combination with leucovorin resulted in a more pronounced inhibition after 48 h (approximately 70%). A significant relationship was observed with outcome of treatment; when thymidylate synthase levels were high and inhibition was low, no response was observed. A separate study showed that low thymidylate synthase levels appeared to be an independent prognostic factor for adjuvant therapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timidilato Sintasa
/
Resistencia a Antineoplásicos
/
Fluorouracilo
/
Antimetabolitos Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Cancer
Año:
1995
Tipo del documento:
Article
País de afiliación:
Países Bajos