Aims: Altered α6β4 integrin expression has been demonstrated in HER-3-negative tumors and may be responsible for anti-HER treatment resistance. The current study aimed to evaluate the interaction between polymorphisms of α6 and β4 integrins and clinical outcome in HER-3-negative, K-RAS wild-type colorectal cancer patients receiving cetuximab. Patients & methods:K-RAS analysis was performed via direct sequencing, HER-3 was evaluated by immunohistochemistry and genotyping of α6 and β4 integrins was performed by real-time PCR. Results: An univariate analysis, the β4 rs8669, rs871443 and rs9367 polymorphisms correlated with progression-free and overall survival. On multivariate analysis, only the β4 rs8669 maintained an independent role in influencing progression-free survival. Conclusion: We believe that β4 rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment. Our findings could also be relevant in planning future trials testing treatment strategies against the integrin-activated molecular pathways. © 2013 Future Medicine Ltd.
Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab / M. Scartozzi, R. Giampieri, C. Loretelli, A. Mandolesi, M. del Prete, S. Biagetti, S. Alfonsi, L. Faloppi, M. Bianconi, A. Bittoni, I. Bearzi, S. Cascinu. - In: FUTURE ONCOLOGY. - ISSN 1479-6694. - 9:8(2013 Jul), pp. 1207-1214. [10.2217/fon.13.72]
Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab
C. Loretelli;
2013
Abstract
Aims: Altered α6β4 integrin expression has been demonstrated in HER-3-negative tumors and may be responsible for anti-HER treatment resistance. The current study aimed to evaluate the interaction between polymorphisms of α6 and β4 integrins and clinical outcome in HER-3-negative, K-RAS wild-type colorectal cancer patients receiving cetuximab. Patients & methods:K-RAS analysis was performed via direct sequencing, HER-3 was evaluated by immunohistochemistry and genotyping of α6 and β4 integrins was performed by real-time PCR. Results: An univariate analysis, the β4 rs8669, rs871443 and rs9367 polymorphisms correlated with progression-free and overall survival. On multivariate analysis, only the β4 rs8669 maintained an independent role in influencing progression-free survival. Conclusion: We believe that β4 rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment. Our findings could also be relevant in planning future trials testing treatment strategies against the integrin-activated molecular pathways. © 2013 Future Medicine Ltd.File | Dimensione | Formato | |
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