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.
Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab / Scartozzi, M; Giampieri, R; Loretelli, C; Mandolesi, A; del Prete, M; Biagetti, S; Alfonsi, S; Faloppi, L; Bianconi, M; Bittoni, A; Bearzi, I; Cascinu, Stefano. - In: FUTURE ONCOLOGY. - ISSN 1479-6694. - 9:(2013), 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
CASCINU, Stefano
2013-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.