Novel approaches to target NF-κB and other signaling pathways in cancer stem cells.

Recently cancer tissue is considered to consist of large number of balk cancer cells and a small number of cancer stem cells. After surgery, radiotherapy, or chemotherapy, most cancer cells are removed, but if there are still very small number of cancer stem cells left. They may form the similar tumor again. So removal of cancer stem cells is considered to be important for future cancer therapy. In one hand, NF-κB is the transcription factor that promotes expressions of various inflammatory cytokines and apoptosis inhibitory proteins. Cancer cells often possess constitutively activated NF-κB that often provides excess survival and therapeutic resistance in cancer cells. We have discovered DHMEQ as a specific inhibitor of NF-κB. This compound was found to be more active in cancer stem cells than in balk cancer cells. In breast cancer cells both PI3K-Akt and NF-κB pathways appear in the survival of cancer stem cells.