Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy.
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.
Wulfkuhle
Julia D
JD
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia 20110, USA. jwulfkuh@gmu.edu
Speer
Runa
R
Pierobon
Mariaelena
M
Laird
Julie
J
Espina
Virginia
V
Deng
Jianghong
J
Mammano
Enzo
E
Yang
Sherry X
SX
Swain
Sandra M
SM
Nitti
Donato
D
Esserman
Laura J
LJ
Belluco
Claudio
C
Liotta
Lance A
LA
Petricoin
Emanuel F
EF
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016000:Cluster Analysis; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007834:Lasers; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D042282:Microdissection / Q000379:methods; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt