Anti-tumor properties of Dickkopf 3b
The invention relates to novel therapeutic approaches to cancer treatment that exploits tumor suppressor functions of DKK3b by site-specific delivery of DKK3b. Novel therapeutics and methods for treating tumors and cancers utilizing DKK3b tumor suppressor functions are disclosed.
1. A method for treating cancer in a subject in need thereof, comprising administering to the subject a pharmaceutical effective amount of a composition comprising a recombinant virus genetically modified to include a nucleic acid sequence consisting of exons 3-8 of the Dkk3 gene functionally linked to a promoter to express human intracellular Dickkopf-3b (DKK3b) protein, and a pharmaceutical acceptable carrier, wherein the cancer is selected from the group consisting of prostate cancer and breast cancer, wherein expression of DKK3b in prostate tumor inhibits tumor growth by inducing JNK phosphorylation and activating JNK-mediated apoptosis, and wherein expression of DKK3b in breast cancer prevents β-catenin from reaching its nuclear TCF target, arrest tumor cell growth and block TCF-driven proliferation/survival signals.
2. The method of claim 1 , wherein the promoter is localized to 250 bases upstream of exon 3 and includes a TATA box in intron 2.
3. The method of claim 1 , wherein the cancer is that of breast.
4. A pharmaceutical composition for treating a cancer selected from the group consisting of prostate cancer and breast cancer, comprising a recombinant virus genetically modified to include a nucleic acid sequence consisting of exons 3-8 of the Dkk3 gene functionally linked to a promoter to express human intracellular Dickkopf-3b (DKK3b) protein, and a pharmaceutical acceptable carrier, wherein expression of DKK3b in prostate tumor inhibits tumor growth by inducing JNK phosphorylation and activating JNK-mediated apoptosis, and wherein expression of DKK3b in breast tumor prevents β-catenin from reaching its nuclear TCF target, arrest tumor cell growth and block TCF-driven proliferation/survival signals.
5. The pharmaceutical composition of claim 4 , wherein the promoter is localized to 250 bases upstream of exon 3 and includes a TATA box in intron 2.