1583pprimary and Acquired Resistance of Colorectal Cancer Cells to Anti-egfr Antibodies Can Be Overcome by the Treatment with Regorafenib in Combination with Cetuximab.
نویسندگان
چکیده
Methods:We have tested, in vitro and in vivo, the effects of regorafenib, a novel oral multikinase inhibitor that targets protein kinases involved in tumor angiogenesis [VEGFR1–3 and tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2)], oncogenesis (KIT, RET and RAF) and the tumor microenvironment [plateletderived growth factor receptor-b and fibroblast growth factor receptor (FGFR)18], in a panel of human CRC cell lines with primary or acquired resistance to cetuximab
منابع مشابه
Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab.
PURPOSE In colorectal cancer, the activation of the intracellular RAS-RAF and PIK3CA-AKT pathways has been implicated in the resistance to anti-EGFR mAbs. We have investigated the role of regorafenib, an oral multikinase inhibitor, in combination with cetuximab, an anti-EGFR mAb, to overcome anti-EGFR resistance. EXPERIMENTAL DESIGN We have tested, in vitro and in vivo, the effects of regoraf...
متن کاملCancer Therapy: Preclinical Primary and Acquired Resistance of Colorectal Cancer toAnti-EGFRMonoclonalAntibodyCanBe Overcome by Combined Treatment of Regorafenib with Cetuximab
Purpose: In colorectal cancer, the activation of the intracellular RAS–RAF and PIK3CA–AKT pathways has been implicated in the resistance to anti-EGFR mAbs. We have investigated the role of regorafenib, an oral multikinase inhibitor, in combination with cetuximab, an anti-EGFRmAb, to overcome anti-EGFR resistance. Experimental Design: We have tested, in vitro and in vivo, the effects of regorafe...
متن کاملPrimary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathway activation and can be overcome by combined MEK/EGFR inhibition.
PURPOSE The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab. EXPERIMENTAL DESIGN We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab. RESULTS Among the colorectal cancer cell lines, five ...
متن کاملCross-Resistance of Acquired Radioresistant Colorectal Cancer Cell Line to gefitinib and regorafenib
Background: Usually, chemoradiotherapy can be used for the treatment of locally advanced colorectal cancer (CRC) before surgery. On the other hand, some studies have shown that fractional radiation of tumor cells leads to chemoresistance. The aim of this study was to evaluate the chemoresistance of radioresistant sub-line (RR sub-line).Methods: This study was done in Hamadan University of...
متن کاملAntitumor efficacy of triple monoclonal antibody inhibition of epidermal growth factor receptor (EGFR) with MM151 in EGFR-dependent and in cetuximab-resistant human colorectal cancer cells
Purpose We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 a...
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ورودعنوان ژورنال:
- Annals of oncology : official journal of the European Society for Medical Oncology
دوره 25 suppl_4 شماره
صفحات -
تاریخ انتشار 2014