Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers

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.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2014
Accession Number
ADA613131

Entities

People

  • Dewey G. Mccafferty

Organizations

  • Duke University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Culture Techniques
  • Epigenetics
  • Estrogens
  • Fragmentation
  • Hormones
  • Inhibition
  • Inhibitors
  • Mass Spectrometry
  • Molecules
  • Neoplasms
  • Protein-Protein Interactions
  • Proteins
  • Proteomics
  • Spectrometry
  • Xenografts

Readers

  • Auditory Neuroscience/Auditory Physiology.
  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech