Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy

J Proteome Res. 2008 Apr;7(4):1508-17. doi: 10.1021/pr7008127. Epub 2008 Feb 8.

Abstract

Phosphoprotein driven cellular signaling events represent most of the new molecular targets for cancer treatment. Application of reverse-phase protein microarray technology for the study of ongoing signaling activity within breast tumor specimens holds great potential for elucidating and profiling signaling activity in real-time for patient-tailored therapy. Analysis of laser capture microdissection primary human breast tumors and metastatic lesions reveals pathway specific profiles and a new way to classify cancer based on functional signaling portraits. Moreover, the data demonstrate the requirement of laser capture microdissection for analysis and reveal the metastasis-specific changes that occur within a new microenvironment. Analysis of biopsy material from clinical trials for targeted therapeutics demonstrates the feasibility and utility of comprehensive signal pathway activation profiling for molecular analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cluster Analysis
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lasers
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Microdissection / methods
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / metabolism
  • Proteomics / methods*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinazolines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • Protein Kinases
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt