Maintenance Treatment with Cetuximab and BAY86-9766 Increases Antitumor Efficacy of Irinotecan plus Cetuximab in Human Colorectal Cancer Xenograft Models.

摘要: Purpose: The use of cetuximab in the treatment metastatic colorectal cancer is limited by development resistance. Experimental Design: We have investigated three models highly epidermal growth factor receptor (EGFR)–dependent xenografts, effect maintenance therapy with different kinase inhibitors alone or combination cetuximab, after cytotoxic induction irinotecan plus cetuximab. Results: SW48, LIM 1215, and GEO cell lines were engrafted into nude mice treated for 3 weeks and/or combined induced a significant reduction tumor size. A subsequent experiment was performed all xenograft which an randomly assigned to one following treatments: control, regorafenib, selective PIK3CA inhibitor (PIK3CAi), MEK (MEKi), each MEKi determined best antitumor activity suppression growth. This prolonged 13 15 cessation accompanied survival. Antitumor inhibition MAPK pathways. Moreover, MEKi-treated SW48 group, KRAS mutations as mechanism acquired resistance detected 25% cases compared 75% group. Conclusions: possible strategy prevent overcome anti-EGFR initial Clin Cancer Res; 21(18); 4153–64. ©2015 AACR .