Enhancement of the Efficacy of Conventional Anticancer Compounds Through the Repression of SNAI Proteins in Aggressive Breast Cancer Cells

Our long-term goal is to understand the impact of high levels of SNAI repressor proteins in the etiology, progression and pathogenicity of breast cancer. Our central hypothesis is that combinatorial treatment of SNAI-high breast tumor cells with the SNAI inhibitors will not only diminish their aggressiveness but also make these cells sensitive to the inhibition of some of the conventional anticancer agents such as vitamin D and anti-estrogens. Specific Aims: (1) To evaluate the levels of SNAI proteins in relation to the levels of the proteins that impart resistance against vitamin D and anti-estrogens in human breast cancer tissues; (2) To determine the effects of alterations of the levels of SNAI proteins in breast cancer cells on their sensitivity towards vitamin D and/or 4HT; and (3) To evaluate the efficacy of RNA and peptide-based inhibitors of SNAI-protein functions on the aggressiveness, metastatic ability and drug sensitivity of SNAI-high human breast cancer cells in a mouse xenograft model.
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