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. 2018 Jul 3;9(51):29654–29664. doi: 10.18632/oncotarget.25664

Figure 4. Anti-tumor activity of ponatinib in CRC PDX models.

Figure 4

In vivo efficacy of ponatinib in RET fusion-positive (CR1520 (A) and CR2518 (B)) and -negative (CR2502 (C) and CR2520 (D)) CRC PDX models. Left panel, Schematic representation of the RET rearrangements: NCOA4-RET (CR1520, top) and CCDC6-RET (CR2518, bottom) fusions as well as the samples with no fusions, which were identified using RNA-seq. From the bottom, an arrow shows the strand of each gene, with the gene structure drawn above. Dashed lines indicate introns not drawn to scale. The pink overlay shows the exons taking part in the fusion. Normalized RNA sequencing coverage is drawn above. Only RET exons included in the fusion are expressed. Middle panel, Ponatinib (20 mg/kg q.d. oral dosing) or 5-FU (40 mg/kg, twice-weekly i.p.) were administered for 28 days to mice bearing patient-derived CRC tumors. Mean tumor volume and SEM are plotted. Statistical significance was calculated using 1-way ANOVA (*P < 0.05) in which each treatment group was compared with its vehicle. Right panel, Pharmacodynamic effect of ponatinib treatment in RET fusion-positive CR1520 and CR2518. Each lane represents a separate animal.