Targeting Micrornas With Small Molecules: A Novel Approach to Treating Breast Cancer
Annual rept. 15 Sep 2009-14 Sep 2010
M D ANDERSON CANCER CENTER HOUSTON TX
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With the discovery, in the last few years, of thousands of genes that produce small non-coding RNAs transcripts with no significant open reading frame named microRNAs miRNAs, it has become evident that the genomic complexity of the cancer cell is far greater than expected. Breast cancer BC is the most common cancer in women and over a third of women with BC will develop metastatic diseases. The broad goal of our research program is to develop an innovative approach of a novel microRNA-based targeted therapy in BC, on the hypothesis that small molecule inhibitors could target miRNAs and this targeting has functional consequences in malignant cells. This proposal focuses on the identification of novel small molecule inhibitors targeting miRNAs using virtual high-throughput screening vHTS approaches. The identified hits will be experimentally validated and the confirmed active hits will be optimized to generate potential leads for further drug development. We already accomplished the first aim, to identify in silico small molecules that target miRNA transcripts. The second aim is under development, the identification of the functional consequences of the interaction between miRNAs and small molecules in BC cells, including cell proliferation, cell death and invasion capacity. Our project already generate preliminary data useful for the basis of a new type of miRNA-based targeted therapy that will benefit BC patients mainly with metastases, by focusing on hits that target miR-10b and miR-21.
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