System of interdependent anticancer antisense oligonucleotides targeting mRNAs the targets of which are NADPH-dependent, combined with one or more inhibitors of the Pentose Phosphate Pathway to deplete NADPH

摘要

It is becoming increasingly clear that the genome and epigenome of another particular cancer cell represents the end product of a vast array of selection events, creating an extremely heterogeneous metabolic landscape. Since genomic and epigenomic variability exists between different cells in a tumor, the target complexity becomes even more extreme when the entire cancer cell population is considered. The only way to overcome this target complexity is by developing complex treatment modalities capable of simultaneously interdicting multiple pathways critical to the growth and survival of the cancer cell population. We have developed a method to couple suppression of NADPH levels (by inhibition of the Pentose Phosphate Pathway) with a system of antisense oligonucleotides targeting NADPH-dependent enzymes critical to the cancer cell. In the preferred embodiment of this invention, the PPP inhibitor is administered systemically, and the antisense oligonucleotides locally, directly to the tumor.

主权项

1. A method of treating cancer in dogs comprising depletion of NADP(H) by inhibition of the Pentose Phosphate Pathway (PPP), combined with one or more antisense oligonucleotides targeting mRNA coding for NADPH-dependent proteins.