Supplementary Figures 1 - 3, Tables 1 - 3 from Primary 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

Abstract

PDF file - 1325KB, Caption Supplementary Figure 1 A and 1B. The combined treatment of cetuximab and the selective MEK1/2 inhibitor BAY 86-9766 induce a synergistic growth inhibitory effects in CRC cell lines with primary and acquired resistance to cetuximab and an antagonistic effects in cetuximab-sensitive CRC cell lines. Caption Supplementary Figure 2. The BAY 86-9766 treatment, in CRC cancer cell lines with primary and acquired resistance to cetuximab, induce a dose dependent reduction of MAPK and MEK phosphorylation. Caption Supplementary Figure 3. The combined treatment of cetuximab and the selective MEK1/2 inhibitor BAY 86-9766 was well tolerated by mice, with no weight loss or other signs of acute or delayed toxicity. Caption Supplementary Table 1A and 1B. The panel of CRC cell lines have been treated with several concentrations of cetuximab and selective MEK1/2 inhibitors (BAY 86-9766, Selumetinib and Pimasertib), showing differential sensitivity to the drugs. Caption Supplementary Table 2. We have performed the experiments on a panel of eight human CRC cell lines having different mutation profiles in KRAS, NRAS, BRAF, PIK3CA and EGFR genes. Caption Supplementary Table 3. In the CRC cell lines with acquired and primary resistance to cetuximab, the treatment with the selective MEK1/2 inhibitor BAY 86-9766 determined synergistic growth inhibitory effects in combination with cetuximab.</p