Testing Grb2 as a Target for Cancer Therapy

Abstract

In breast cancers with erbB-2 overexpression abnormal cell proliferation is caused by the extremely active tyrosine kinase activity and resulting high level of signal transduction. An early and important intermediate in this signalling is the adaptor protein Grb2. This application proposed to design and test novel Grb2 inhibitors. This analysis will have important implications for translational cancer research by testing Grb2 inhibition as a target for therapy using compounds of defined biochemical activity. The support from USAMRMC for the peptide based studies has led to development of modified peptidomimetics and small molecule inhibitors and successful funding from the Komen Foundation for Breast Cancer Research. The results from the peptide Grb2 inhibitors study provided an important proof-of-concept for an approach that may generate specific, potent SH2 antagonists as clinical candidates in the near future. This type of SH2 antagonists might have a better therapeutic potential to be used either by themselves or in combination with other conventional chemotherapeutics in the treatment of breast cancer.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2001
Accession Number
ADA405163

Entities

People

  • Dajun Yang

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Biotechnology
  • Breast Cancer
  • Chemical Synthesis
  • Chemistry
  • Inhibition
  • Inhibitors
  • Liquid Chromatography
  • Mass Spectrometry
  • Molecules
  • Neoplasms
  • Organic Chemistry
  • Small Molecules
  • Surface Plasmon Resonance
  • Surface Plasmons
  • Therapy

Readers

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