Fig. 4.

Pamiparib potentiates temozolomide in both naive and TMZ-resistant H209 cells and in a xenograft mouse model. (A and B) IC₅₀ curves in H209 and H209 TMZ resistance (H209-TR) cell lines. H209-TR cell lines were generated from H209 tumors by treatment with multiple cycles of TMZ in vivo. The derived H209-TR cells remained sensitive to the combination of pamiparib and TMZ in vitro. (C) The combined activity of pamiparib and TMZ in the H209 SCLC xenograft model. TMZ as a single agent was quite effective in this H209 model. One cycle of treatment resulted in all animals becoming tumor-free. However, resistance occurred quickly during the second cycle. Pamiparib and TMZ together significantly prevented resistance, and tumors remained sensitive to the drug combination after three cycles of 5-day treatment. (D) Synergistic activity of pamiparib and TMZ in the H209-TR xenograft model. TMZ single treatment was not effective in this model. In contrast, pamiparib and TMZ combination treatment was efficacious during two cycles of treatment.