Synergistic interaction of olaparib and cisplatin

In vitro profiling confirms clinically approved combinations

  • Olaparib (Lynparza®), a PARP inhibitor, is an FDA-approved drug for use in several epithelial cancers that are sensitive to platinum-based chemotherapy.
  • PARP inhibitors synergize with platinum-based chemotherapy by preventing the repair of platinum-induced DNA damage.
  • In the NTRC Oncolines™ pan-cancer panel, the T-ALL cell line MOLT-4 is among the most sensitive to olaparib, consistent with findings that PARP inhibition could be of therapeutic relevance in T-ALL [1,2].

  • As expected, olaparib and cisplatin were found to have synergistic interaction in MOLT-4 cells.

  • The interaction occurred at all the evaluated compound ratios and all efficacy levels, indicating a robust synergy (see chart with CI values).

SynergyFinder_olaparib + cisplatin_15SF113
SynergyFinder Olaparib + Cisplatin CI 15SF113
SynergyFinder Olaparib + Cisplatin CI 15SF113
Fixed-ratio combination experiment of olaparib and cisplatin in MOLT-4 cells. The curves of the mixtures (red, orange, pink) show a shift to the left compared to the single agent curves (green, blue), indicating synergy. This is confirmed by the CI-values that are < 1 (right, above) and the isobologram (left, below).

References

1. Esposito et al. (2015) Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors. Nature Medicine 21:1481-1490.

2. Dasgupta et al. (2018) Drugging DNA repair to target T-ALL cells. Leukemia & Lymphoma 59, 1746–1749.