Mixed Lineage Kinases as Novel Targets for the Treatment of Endocrine-Resistant, ER-Positive Breast Cancer

Abstract

Previous research in our laboratory has demonstrated that a small molecule inhibitor of Mixed Lineage Kinases (MLKs) induces a cell cycle arrest and apoptosis in estrogen receptor (ER) - positive breast cancer cells in culture, while having minimal effects on non-tumorigenic mammary epithelial cells. The overall goal of the current research is to test the efficacy of this inhibitor in pre-clinical mouse xenograft models of human ER positive breast cancer. During the current reporting period, we developed an accurate and sensitive mass spectrometry based method for detection of the compound in mouse serum and tissue, and optimized conditions for administration of the drug to animals. We also established methods for monitoring tumor growth using both cell lines and patient derived xenografts in immune compromised mice. Experiments are in progress to test the ability of the MLK inhibitor to block the growth of endocrine sensitive and endocrine resistant human breast cancer cell lines and patient derived xenografts in these pre-clinical mouse models.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2016
Accession Number
AD1019348

Entities

People

  • Susan E. Conrad

Organizations

  • Michigan State University

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Biomedical Research
  • Breast Cancer
  • Carcinoma
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Detection
  • Estrogens
  • Inhibitors
  • Liquid Chromatography
  • Mass Spectrometry
  • Neoplasms
  • Small Molecules
  • Spectrometry
  • Tumor Cell Line
  • Xenografts

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).