Preclinical data suggested that, in the presence of human epidermal growth factor receptor (HER)-3-altered activation, colorectal cancer cells may escape anti-epidermal growth factor receptor (EGFR)-mediated cell death. HER-3 overexpression may then represent a key factor for resistance to anti-EGFR antibodies in colorectal cancer. The aim of our analysis was to investigate a possible correlation between HER-3 expression and clinical outcome in wild-type K-RAS advanced colorectal cancer patients receiving cetuximab and irinotecan. We retrospectively analyzed immunoreactivity for HER-3 in wild-type K-RAS advanced colorectal cancer patients receiving irinotecan and cetuximab. Eighty-four advanced wild-type K-RAS colorectal cancer patients were available for HER-3 analysis. Forty patients (48\%) had a HER-3(-) colorectal tumor, whereas the remaining 44 cases (52\%) were deemed HER-3(+). In patients with HER-3(-) and HER-3(+) tumors, we observed a partial response in 17 (42\%) and eight (18\%) patients respectively; progressive disease occurred in 11 (35\%) and 26 (53\%) patients with HER-3(-) and HER-3(+) tumors, respectively (p = .003). The median progression-free survival time was 6.3 months in patients with HER-3(-) tumors and 2.8 months for those who had HER-3-overexpressing tumors (p < .0001). The median overall survival time was 13.6 months in patients showing HER-3(-) tumors and 10.5 months for those who had HER-3-expressing tumors (p = .01). HER-3 proved to be a predictive factor for clinical outcome in wild-type K-RAS colorectal cancer patients treated with cetuximab. Combined HER-3 and K-RAS analysis may represent an effective strategy for better selection of responding colorectal cancer patients.
|Data di pubblicazione:||2011|
|Titolo:||The role of HER-3 expression in the prediction of clinical outcome for advanced colorectal cancer patients receiving irinotecan and cetuximab.|
|Autori:||Scartozzi M.; Mandolesi A.; Giampieri R.; Bittoni A.; Pierantoni C.; Zaniboni A.; Galizia E.; Giustini L.; Silva R.R.; Bisonni R.; Berardi R.; Biscotti T.; Biagetti S.; Bearzi I.; Cascinu S.|
|Digital Object Identifier (DOI):||10.1634/theoncologist.2010-0119|
|Appare nelle tipologie:||Articolo su rivista|
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