Supplementary Materials

Supplementary Material for:

Blockade of EGFR and MEK Intercepts Heterogeneous Mechanisms of Acquired Resistance to Anti-EGFR Therapies in Colorectal Cancer

Sandra Misale, Sabrina Arena, Simona Lamba, Giulia Siravegna, Alice Lallo, Sebastijan Hobor, Mariangela Russo, Michela Buscarino, Luca Lazzari, Andrea Sartore-Bianchi, Katia Bencardino, Alessio Amatu, Calogero Lauricella, Emanuele Valtorta, Salvatore Siena, Federica Di Nicolantonio, Alberto Bardelli*

*Corresponding author. E-mail:

Published 19 February 2014, Sci. Transl. Med. 6, 224ra26 (2014)
DOI: 10.1126/scitranslmed.3007947

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Mutational profiling of candidate genes in resistant cells.
  • Fig. S2. Gene copy number (GCN) analysis in resistant cells.
  • Fig. S3. KRAS amplification in parental and resistant NCIH508 and HCA-46 cell lines.
  • Fig. S4. Measurement of RAS activation in resistant cells.
  • Fig. S5. Biochemical validation of siRNA-mediated gene knockdown.
  • Fig. S6. Pharmacological inhibition of MEK in cells resistant to anti-EGFR blockade.
  • Fig. S7. Pharmacological inhibition of EGFR or MEK1/2 with cetuximab or pimasertib.
  • Fig. S8. Sensitivity to combinatorial EGFR and MEK inhibition in a mouse xenograft from a metastatic CRC patient who relapsed after anti-EGFR therapy.
  • Table S1. Frequencies of mutant alleles in resistant cell lines assessed by BEAMing.
  • Table S3. List of primers for gene amplification and sequencing.
  • Table S4. List of primers and probes for BEAMing analysis.
  • Table S5. List of primers for gene copy number analysis by real-time PCR.
  • Table S6. List of siRNAs.
  • References (4245)

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Other Supplementary Material for this manuscript includes the following:

  • Table S2. (separate Excel file) Tabular data for NCIH508 R-cetux and OXCO-2 R1-cetux xenograft measurements, as well as PDX measurements.

[Table S2]