Treatment of cancer and cancer stem cells by blocking the Notch pathway.

2539 Background: Current treatments often fail to cure cancer. It has been shown (JCO, 26, June 10, 2008) that Cancer Stem Cells, (CSCs), are responsible for the initiation, metastasis and recurrence of many cancers and may be a key reason for the failure of current therapies.The NOTCH pathway is an important pathway in the development of many tumors ,and cancer stem cells in particular. Methods: We have generated genetically and synthetically a hybrid protein (Antp-DNMAML) .consisting of the truncated version of MastermindElike (MAML) that behaves in a dominant negative (DN) fashion inhibiting Notch activation, and the cell penetrating peptide Antennapedia (Antp). Results: It is demonstrated that Antp-DNMAML translocates into the nucleus and suppresses Notch activation. Attenuation of Notch signaling with AntpEDNMAML reverts the transformed phenotype, inhibits the anchorageEdependent growth, induces self contact inhibition and apoptosis in highly tumorigenic epithelial human breast cancer cells. More sig...