Combinations of Bevacizumab and Erlotinib Show Activity in Colorectal Cancer Independent of RAS Status

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Paul MésangeAnnette K Larsen

Abstract

Purpose: There is extensive cross-talk between VEGF- and EGFR-pathway signaling in colorectal cancer. However, combinations of VEGF- and EGFR-targeted monoclonal antibodies (mAb) show disappointing activity, in particular for patients with mutant RAS Previous results show that tyrosine kinase inhibitors (TKI) can be active in colorectal cancer models resistant to mAbs. This prompted us to examine whether the activity of bevacizumab can be increased by combination with erlotinib.Experimental Design: The antitumor activity of bevacizumab, erlotinib, and their combination was determined in colorectal cancer models with different RAS status and bevacizumab sensitivity. EGFR/VEGF pathway activation was characterized by immunohistochemistry, Western blot, and ELISA assays. The influence of cetuximab and erlotinib on EGF-mediated migration and the EGFR-EGF ligand feedback loop was established in colorectal cancer cell lines with different RAS status.Results: The addition of erlotinib increased bevacizumab activity in all models independent of RAS status. Bevacizumab exposure was accompanied by marked EGFR activation in tumor cells as well as in tumor-associated endothelial cells (TECs) and resulted in strong accumulation of intracellu...Continue Reading

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Citations

May 10, 2019·Scientific Reports·Marloes ZoetemelkPatrycja Nowak-Sliwinska
Dec 20, 2019·Dose-response : a Publication of International Hormesis Society·Zhi HuangSha-Sha Peng
Oct 1, 2021·Experimental & Molecular Medicine·Man-Seok JuSang Taek Jung

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