Abstract: Antisense 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. The invention further relates to a combination product comprising an antisense oligonucleotide in combination with an anticancer agent such as Tomudex or pemetrexed and to the use of such a combination product in the treatment of cancer.

Abstract: The invention relates to deoxyribo- and ribo-oligonucleotides and derivatives thereof, as well as pharmaceutical preparations, therapies, diagnostics and commercial research reagents in relation to disease states which respond to modulation of the synthesis of the enzyme S-adenosylmethionine decarboxylase (SAMDC). In particular, the invention relates to antisense oligonucleotides and oligonucleotide derivatives specifically hybridizable with nucleic acids relating to (preferably human) SAMDC. These oligonucleotides and their derivatives have been found to modulate the synthesis of SAMDC in cells.