Targeting micrornas for the treatment of liver cancer

A - Human Necessities – 61 – K

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A61K 31/7105 (2006.01) A61P 35/00 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2704043

Provided herein are methods for the treatment of liver cancer. These methods encompass the administration of a compound comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Also provided herein are compositions for the treatment of liver cancer. Such compositions include compounds comprising a modified oligonucleotide, wherein the modified oligonucleotide is targeted to a miRNA. Certain miRNAs have been identified as overexpressed in liver cancer, such as, for example, hepatocellular carcinoma, and are thus selected for targeting by modified oligonucleotides. Further, certain miRNAs have been identified as overexpressed in hepatocellular carcinoma cells exposed to dioxin, and are thus selected for targeting by modified oligonucleotides. Antisense inhibition of certain of these miRNAs has been found to inhibit cell proliferation and induce apoptosis.

L'invention porte sur des procédés pour le traitement du cancer du foie. Ces procédés comprennent l'administration d'un composé comprenant un oligonucléotide modifié, l'oligonucléotide modifié étant ciblé sur un miARN. L'invention porte également sur des compositions pour le traitement du cancer du foie. De telles compositions comprennent les composés comprenant un oligonucléotide modifié, l'oligonucléotide modifié étant ciblé sur un miARN. Certains miARN ont été identifiés comme étant surexprimés dans le cancer du foie, tel que, par exemple, un carcinome hépatocellulaire, et sont ainsi sélectionnés pour un ciblage par des oligonucléotides modifiés. En outre, certains miARN ont été identifiés comme étant surexprimés dans des cellules de carcinome hépatocellulaire exposées à la dioxine, et sont ainsi sélectionnés pour un ciblage par des oligonucléotides modifiés. On a découvert qu'une inhibition anti-sens de certains de ces miARN peut inhiber la prolifération cellulaire et induire l'apoptose.

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