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Decoy Oligonucleotides Corresponding to NF-KappaB Binding Site in MGMT Promoter for Cancer Treatment and Drug Resistance. (Hadasit)

Summary

Alkylating agents are the most widely used anticancer drugs. Drug resistance is a major obstacle in the successful treatment of cancer by alkylating agents.
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) has been implicated in resistance of human tumors to alkylating agents. The expression level of MGMT is regulated by NF-kappaB. Interference with the binding of NF-kappaB to MGMT promoter could reverse MGMT-induced chemoresistance. The present invention provides modified decoy oligonucleotides corresponding to NF-KappaB binding site within MGMT promoter as a novel approach for sensitizing tumor cells to alkylating agents. The decoy oligonucleotides can effectively reverse chemoresistance in several cancer cell lines.

Technology Benefits

Specific target: the drug specifically target MGMT, the main cause for resistance to alkylating agents. Specific NF-kappaB oligonucleotide decoy: we are using a unique oligonucleotide that binds to a specific NF-KappaB site within MGMT promoter. We anticipate that the proposed decoy would exhibit less toxicity in comparison to other methods which target a general NF-kappaB binding site.

Technology Application

The drug could be used widely to overcome the resistance to chemotherapy in most cancer patients including, brain tumors, melanoma, lymphoma, myeloma, leukemia and sarcoma.

ID No.

8-2010-9

Country/Region

Israel

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