Figure 5. VX-970 inhibits ATR and promotes sustained regression in a human primary lung tumor xenograft.

(A) Mice bearing OD26749 tumors were treated with a single dose of VX-970 (60 mg/kg PO) and cisplatin (3 mg/kg IP) either as monotherapy or in combination. P-Chk1 and P-H2AX were analyzed by western blot 4 and 48 h after treatment, respectively, and were corrected to total H2AX levels. (B) Representative PET/CT images of mice at baseline (top row) and six days following the indicated treatment (bottom row). Concentration of ¹⁸FLT is indicated by the intensity of the orange color in the PET image. An X-ray CT image of the skeletal system (white) is superimposed for anatomical reference. The tumor is circled (green). Treatment with VX-970 alone had no discernable effect on PET signal (image not shown). (C) Average standard uptake value (SUV) of ¹⁸FLT. (D) Tumor size changes as determined by CT. (E) Examination of prognostic value of ¹⁸FLT imaging. (F) Assessment of the durability of response to VX-970. OD26749 tumors were passaged in SCID mice to P4. Treatment started when the average tumor size was approximately 200 mm³. Tumor bearing mice were treated with vehicle, VX-970 alone (60 mg/kg PO, 4 consecutive days a week), cisplatin alone (3 mg/kg, IP, q7d) and the combination, for two weeks. Vehicle and VX-970 groups were terminated after the final dose of VX-970. Following treatment discontinuation, tumor growth in the cisplatin alone and combination groups was followed twice a week until the average tumor volume reached 1000 mm³. The arrowhead on the graph marks the end of treatment. Error bars are standard errors for all graphs.