Decoy Oligonucleotides Corresponding to NF-KappaB Binding Site in MGMT Promoter for Cancer Treatment and Drug Resistance. (Hadasit)
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.
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.
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.
8-2010-9
以色列
