Figure 2

Cancer signaling pathways affected within the tumor. (a) Pre-treatment: overall, the down-regulation of PTEN and up-regulation of the RET signaling pathway appear to be driving tumor proliferation. Increased signaling independent of EGFR is consistent with the observed erlotinib insensitivity of the tumor. (b) Post-versus pre-treatment: after treatment with the RET inhibitors sunitinib and sorafenib, there is a marked increase in the signaling of pathway constituents, increasing tumor proliferation. Black and red pathway arrows represent activation and inhibition, respectively. Dotted arrows represent indirect interactions. The number of arrows denoting significantly over- or under-expressed genes are quantified using fold change of tumor versus compendium in (a), and primary tumor versus the tumor recurrence in (b): 1 arrow is FC ≥2; 2 arrows is FC ≥10; and 3 arrows is FC ≥50. CNV, copy number variation.