In this article , which was published in the February 15, 2015, issue of Clinical Cancer Research (1), panels A–C of Fig. 4 are identical to panels A–C of Fig. 3. In addition, the first sentence of the Fig. 4 legend erroneously lists “ES-6”; it should be “EW-5.” A new version of Fig. 4, including the correct versions of panels A–C, and the revised legend are provided below. The authors regret this error.
Pharmacodynamic changes induced by talazoparib and temozolomide in nonresponsive xenograft lines EW-8 and EW-5. Maintenance of PARP is associated with intrinsic resistance to temozolomide (TMZ)/talazoparib (TAL) combinations in vivo. EW-8 (A) and EW-5 (B) xenograft tissues (n = 3) were harvested after 5-day temozolomide (12 mg/kg/d), talazoparib (0.25 mg/kg twice daily, 9 doses), or the combination and processed as described in Materials and Methods. Immunoblots were probed for PARP, cleaved PARP, γH2AX, and GAPDH (loading control). C, PARP levels in control tumors (n = 3); D, Talazoparib alone or the combination of temozolomide and talazoparib decreases PARP transcripts in sensitive xenograft models. PARP transcripts (normalized to GAPDH transcripts) were determined by qRT-PCR in control tumors, and tumors harvested 6 hours after dosing on day 5 treatment with temozolomide (12 mg/kg) and talazoparib (0.25 mg/kg). E, Development of TC-71 xenografts resistant to combination B. Resistance was developed as described in Materials and Methods. The response of individual naïve parental TC-71 tumors (designated pass R0), pass R1 (the second drug treatment), pass R3, and pass R5 is shown. The relative tumor volume plots (right) show the growth of the median tumor for each group (gray, control; black, treated). Note that in pass 0, 10 tumor-bearing mice were treated, and the median tumor volume at 6 weeks was <0.1 cm3. For other groups, 5 tumor-bearing mice were in the treatment groups. F, Western blot analysis for PARP, cleaved PARP, and γH2AX for TC-71 parental xenografts (untreated), control (untreated) TC-71R, and treated TC-71R xenografts.
Pharmacodynamic changes induced by talazoparib and temozolomide in nonresponsive xenograft lines EW-8 and EW-5. Maintenance of PARP is associated with intrinsic resistance to temozolomide (TMZ)/talazoparib (TAL) combinations in vivo. EW-8 (A) and EW-5 (B) xenograft tissues (n = 3) were harvested after 5-day temozolomide (12 mg/kg/d), talazoparib (0.25 mg/kg twice daily, 9 doses), or the combination and processed as described in Materials and Methods. Immunoblots were probed for PARP, cleaved PARP, γH2AX, and GAPDH (loading control). C, PARP levels in control tumors (n = 3); D, Talazoparib alone or the combination of temozolomide and talazoparib decreases PARP transcripts in sensitive xenograft models. PARP transcripts (normalized to GAPDH transcripts) were determined by qRT-PCR in control tumors, and tumors harvested 6 hours after dosing on day 5 treatment with temozolomide (12 mg/kg) and talazoparib (0.25 mg/kg). E, Development of TC-71 xenografts resistant to combination B. Resistance was developed as described in Materials and Methods. The response of individual naïve parental TC-71 tumors (designated pass R0), pass R1 (the second drug treatment), pass R3, and pass R5 is shown. The relative tumor volume plots (right) show the growth of the median tumor for each group (gray, control; black, treated). Note that in pass 0, 10 tumor-bearing mice were treated, and the median tumor volume at 6 weeks was <0.1 cm3. For other groups, 5 tumor-bearing mice were in the treatment groups. F, Western blot analysis for PARP, cleaved PARP, and γH2AX for TC-71 parental xenografts (untreated), control (untreated) TC-71R, and treated TC-71R xenografts.
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