Destabilization of Abnormal Methylation Enzymes: Nature’s Way to Eradicate Cancer Stem Cells

Over that past decade it has becomes clear that CSCs stand in the way of successful curative results from conventional cytotoxic cell killing to put cancer away. The transition of the tumor to one containing predominantly CSCs is now thought to be a primary cause of treatment failure [1-5]. Many biological characteristics that enable cancer progression are attributable to CSCs, including angiogenesis, metastasis, and drug resistance. CSCs are resistant to both cytotoxic drugs and radiation in part because these cells overexpress ATP binding cassette drug pumps that effectively exclude cytotoxic drugs and have activation of anti-apoptosis programs that negate the pro-apoptotic signals activated by DNA damaging agents [6-9]. CSCs share much in common with normal progenitor stem cells with respect to cell features and biological missions. Their biological missions are to repair and to meet the replacement needs of the organ or tissue. When cancer cells are destroyed by cytotoxic drugs or radiation, CSCs proliferate to replace the dying cancer cells and the tumor regrows. Eventually CSCs become the dominant tumor component and their unchecked growth claims the life of the patient. Therefore, eventual successful cancer therapies must rely on the elimination of not only cancer cells, but also the subpopulation of CSCs. Alternative therapeutic strategies are needed to eradicate CSCs. Methylation Enzymes (MEs) Function as A Switch to Turn on to Cell Replication and to Turn Off to Terminal Differentiation (TD)