Figure 3.

Differential sensitivity among CRC subtypes to cetuximab. (a) Heatmap showing individual responses of patients with metastatic CRC (Khambata-Ford data set³²) to cetuximab treatment and their association with subtypes. (b) Cetuximab response in CRC subtype–specific cell lines is plotted as percentage of proliferation of treated cells (cetuximab, 62.5 µg ml⁻¹) normalized to vehicle-treated control. (c) Cetuximab response in transit-amplifying sub-subtype specific cell lines are plotted as percentage colony formation of treated cells (cetuximab, 15.6 µg ml⁻¹) normalized to vehicle-treated cells. (d–g) Cetuximab response in transit-amplifying sub-subtype–specific xenograft tumors using the CS-TA cell lines NCI-H508 (d) and SW1116 (e) and the CR-TA cell lines LS1034 (f) and SW948 (g). (h) Heatmap depicting differential gene expression patterns and the KRAS mutation status between CR-TA and CS-TA subtypes (Khambata-Ford data set). (i) Kaplan-Meier curve of differential DFS based on FLNA expression in transit-amplifying subtype samples (Khambata-Ford data set). The expression of FLNA was median-centered across all the 80 samples that belong to different subtypes; those above median were considered as ‘FLNA high’, and those below the median were considered as ‘FLNA low’. (j) Differential response to the cMET inhibitor PHA-665752 (625 nM) in CR-TA and CS-TA subtype-specific cell lines, plotted relative to vehicle-treated cells. Error bars represent the s.d. of technical replicates (triplicates in b,c and j, where as the sample sizes are indicated for d–g in the figure) from a representative experiment. *P < 0.05.