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).

[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.

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).