Characterizing SHP2 as a Novel Therapeutic Target in Breast Cancer

Abstract

The Src homology 2-containing protein tyrosine phosphatase (SHP2) is a positive regulator of cellular signaling and promotes breast cancer tumorigenesis. Because of this, it was hypothesized that SHP2 may be a useful therapeutic target in disease, since it acts as an integrator of numerous signaling pathways that are known to be dysregulated in cancer such as HER2. Previous cell biology work has demonstrated that SHP2 is required for maintenance of transformation. It has not been conclusively demonstrated that SHP2 would serve as an attractive therapeutic target. In addition, SHP2 inhibitors designed so far have failed to demonstrate selectivity over closely-related homologues such as SHP1 (1,2). This work was designed to first determine how SHP2 selectively binds its target substrates and then to apply this knowledge in the first-in-class demonstration of SHP2 s viability as a therapeutic target in breast cancer.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2013
Accession Number
ADA573185

Entities

People

  • Zachary C Hartman

Organizations

  • West Virginia University

Tags

Communities of Interest

  • Energy and Power Technologies

DTIC Thesaurus Topics

  • Acidic Amino Acids
  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cells
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Diseases And Disorders
  • Inhibition
  • Inhibitors
  • Neoplasms
  • Peptides
  • Substrates
  • Tyrosine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Systems Analysis and Design