Combinations of Bevacizumab and Erlotinib show activity in colorectal cancer independent of RAS status

摘要: Purpose: There is extensive cross-talk between VEGF- and EGFR-pathway signaling in colorectal cancer. However, combinations of EGFR-targeted monoclonal antibodies (mAb) show disappointing activity, particular for patients with mutant RAS Previous results that tyrosine kinase inhibitors (TKI) can be active cancer models resistant to mAbs. This prompted us examine whether the activity bevacizumab increased by combination erlotinib.Experimental Design: The antitumor bevacizumab, erlotinib, their was determined different status sensitivity. EGFR/VEGF pathway activation characterized immunohistochemistry, Western blot, ELISA assays. influence cetuximab erlotinib on EGF-mediated migration EGFR-EGF ligand feedback loop established cell lines status.Results: addition all independent status. Bevacizumab exposure accompanied marked EGFR tumor cells as well tumor-associated endothelial (TECs) resulted strong accumulation intracellular EGFR, which could attenuated erlotinib. In cellular models, able attenuate functions while only showed wild-type cells.Conclusions: These should provide a molecular framework better understand bevacizumab-erlotinib combination, compared alone, GERCOR DREAM phase III clinical trial. Differential mAbs TKIs targeting same likely applicable other types. Clin Cancer Res; 24(11); 2548-58. ©2018 AACR.