Antisene oligonucleotides targeted to sequences in thymidylate synthase
(TS) mRNA. In particular the invention relates to antisense
oligonucleotides targeted to sequences in the 3' end of TS mRNA, which
are both cytostatic on their own when administered to human tumour cell
lines, and which also enhance the toxicity of anticancer drugs such as
Tomudex. The invention also relates to antisense oligonucleotides
targeted to sequences at or near the translation start site at the 5' end
of TS mRNA which induce TS gene transcription and enhance cell growth.
The invention further relates to a combination product comprising an
antisense oligonucleotide in combination with an anticancer agent such as
Tomudex (N-(5[N-3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methyl-
amino]-2-thenoyl)-L-glutamic acid) or the Zeneca development compound ZD
9331 ((S)-2-(2-fluoro-4-[N-(4-hydroxy-2,7-dimethylquinazolin-6-ylmethyl)--
N-(prop-2-ynyl)amino] benzamido-4-(1H-1,2,3,4-tetrazol-5-yl) butyric
acid), and to the use of such a combination product in the treatment of
cancer.