The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins.
ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy.
Smith
B L
BL
Cell Signaling Technology, 166B Cummings Center, Beverly, MA 01915, USA.
Chin
D
D
Maltzman
W
W
Crosby
K
K
Hortobagyi
G N
GN
Bacus
S S
SS
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D020893:Receptor, ErbB-3 / Q000235:genetics*; D012189:Retrospective Studies; D015398:Signal Transduction; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000068878:Trastuzumab