1. Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy.
- Author
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Wulfkuhle JD, Speer R, Pierobon M, Laird J, Espina V, Deng J, Mammano E, Yang SX, Swain SM, Nitti D, Esserman LJ, Belluco C, Liotta LA, and Petricoin EF 3rd
- Subjects
- Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cluster Analysis, Erlotinib Hydrochloride, Female, Humans, Lasers, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Liver Neoplasms secondary, Microdissection methods, Phosphoproteins metabolism, Phosphorylation, Protein Kinase Inhibitors therapeutic use, Protein Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Quinazolines therapeutic use, Receptor Protein-Tyrosine Kinases metabolism, Breast Neoplasms metabolism, Intracellular Signaling Peptides and Proteins metabolism, Proteomics methods, Signal Transduction
- 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.
- Published
- 2008
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