Accession Number : ADA613131


Title :   Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers


Descriptive Note : Annual rept. 30 Sep 2013-29 Sep 2014


Corporate Author : DUKE UNIV DURHAM NC


Personal Author(s) : McCafferty, Dewey G


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a613131.pdf


Report Date : Oct 2014


Pagination or Media Count : 9


Abstract : Our goals for this project are to explore LSD1 inhibition of protein-protein interactions as a potential therapy for ERalpha breast cancer, ameliorating iLCC for in vivo use, and using novel proteomics approaches to identify coregulatory proteins interacting with ER and LSD1 in ERalpha+ cells and deduce how the complement of LSD1 associating proteins change in ERalpha cancers. We have made significant progress on the aims this project, specifically by completing xenograft studies of iLCC expression and its effect on breast cancer tumor growth and on histone demethylase inhibition. We have made progress on synthesis of selective nonpeptidic LSD1 inhibitors and have initiated studies to identify optimal candidate sequences for stapled peptide analogues of iLCC. Lastly, we have conducted a detailed analysis of LSD1 fragmentation by ESI-MS and have used H/D exchange to identify the binding interface between LSD1 and a partner protein in preparation for interrogating communication between this protein and the ER. At this time there are no changes proposed for the Statement of Work.


Descriptors :   *BREAST CANCER , *ESTROGENS , *RECEPTOR SITES(PHYSIOLOGY) , *THERAPY , CHEMICAL ANALOGS , HISTONES , IN VIVO ANALYSIS , NEOPLASMS , PEPTIDES , PROTEINS , SEQUENCES , SYNTHESIS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE