Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab. (August 2013)

• Record Type: Journal Article
• Authors: Scartozzi, Mario; Giampieri, Riccardo; Loretelli, Cristian; Mandolesi, Alessandra; Prete, Michela del; Biagetti, Simona; Alfonsi, Simona; Faloppi, Luca; Bianconi, Maristella; Bittoni, Alessandro; Bearzi, Italo; Cascinu, Stefano
• Is Part Of: Future oncology. Volume 9:Number 8(2013)
• Page Start: 1207
• Page End: 1214
• Publication Date: 2013-08
• Subjects: cetuximab -- colorectal tumors -- EGFR -- HER-3 -- integrins; Oncology -- Periodicals; 616.99405
• DOI: 10.2217/fon.13.72
• Languages: English
• ISSNs: 1479-6694

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.