Combinatorial methods for inducing cancer cell death

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/63 (2006.01) A61K 35/00 (2006.01) A61K 38/00 (2006.01) A61K 38/17 (2006.01) A61K 48/00 (2006.01) C07H 21/04 (2006.01) C07K 14/47 (2006.01) C12N 15/11 (2006.01) C12Q 3/00 (2006.01)

Patent

CA 2457321

The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K- ras gene, together with introducing an expressible mda-7 gene, in pancreatic cancer cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.

La présente invention concerne des procédés et des compositions permettant de bloquer la prolifération et d'induire la mort cellulaire dans une population de cellules cancéreuses. Ce procédé implique (i) d'augmenter la quantité de protéines <I>MDA</I>-7 associées à la différentiation, et (ii) de diminuer l'activité RAS dans cette population. On s'appuie à cet effet sur la découverte que la diminution d'expression d'un gène à K-ras muté et activé, accompagné de l'introduction dans un gène mda-7, dans les cellules cancéreuses du pancréas, a eu un effet inhibiteur de croissance et anti-survie, et a aboli la tumogénicité des cellules chez les souris nudes privée de thymus. Les procédés de l'invention peuvent s'appliquer au traitement des cancers du pancréas et autres tumeurs.

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