Accession Number : ADA538185


Title :   Targeting Micrornas With Small Molecules: A Novel Approach to Treating Breast Cancer


Descriptive Note : Annual rept. 15 Sep 2009-14 Sep 2010


Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX


Personal Author(s) : Calin, George A ; Zhang, Shuxing ; Priebe, Waldemar


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a538185.pdf


Report Date : Oct 2010


Pagination or Media Count : 14


Abstract : 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.


Descriptors :   *BREAST CANCER , DISEASES , TARGETING , GENES , FRAMES , HYPOTHESES , INHIBITORS , DRUGS , DEATH , CELLS(BIOLOGY) , WOMEN , RIBONUCLEIC ACIDS , METASTASIS , CAPACITY(QUANTITY) , MOLECULES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE