Supplementary Figure Legends 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

PDF file - 116KB</p

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

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

Supplementary Figure 1 from Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy

Bland-Altman plot % increase in cetuximab-mediated ADCC: difference SRB assay-Cytotox96 vs average. By plotting the difference between the % ADCC increase determined by each of the methods against the mean of the two determinations it is possible to determine the concordance between both methods. The limits of agreement are also calculated to give a quantitative analysis of the differences between both methods.</p

Supplementary Figure 1 from Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

PDF file 1732K, Development and characterization of cetuximab-resistant SW48 (SW48-CR) colon cancer cells</p

Supplementary Data from Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy

Figure Legends</p

Supplementary Figure 2 from Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy

Progression-free survival was defined as time elapsed between treatment initiation and clinical progression. PFS was 10.8 months in patients whit FcγRIIIa-V158F or FcγRIIIa-V158V vs 5.1 months in patients whit FcγRIIIa-F158F. Log-Rank test for two curves: p=0.050.</p

Supplementary Table 1 from Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

PDF file 184K, genes up regulated in GEO-CR versus GEO</p

Supplementary Figure 2 from Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

PDF file 1516K, Inhibition of MET expression restores cetuximab sensitivity in SW48-CR cells</p

Supplementary Figure Legend from Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

PDF file 84K, Supplementary figure legend</p

Supplementary Table 2 from Increased TGF-α as a Mechanism of Acquired Resistance to the Anti-EGFR Inhibitor Cetuximab through EGFR–MET Interaction and Activation of MET Signaling in Colon Cancer Cells

PDF file 145K, genes down regulated in GEO-CR versus GEO</p