Exposure to escalating olaparib does not induce acquired resistance to PARPi and to other chemotherapeutic compounds in ovarian cancer cell lines.

Poly (ADP‑ribose) polymerase (PARP)‑inhibitors (PARPi) such as olaparib and niraparib are currently used as a treatment option for ‑deficient tumors and also show efficacy in platinum‑sensitive tumors. However, resistance to PARPi occurs in numerous patients and in particular acquired PARPi resistance presents a major obstacle in the treatment of these tumors. In the present study, it was investigated whether stepwise exposure of ovarian cancer cells to escalating concentrations of olaparib produced subcells with acquired resistance to PARPi and/or acquired cross‑resistance to platinum compounds, paclitaxel, and doxorubicin. To this aim, the sensitivity of fourteen ovarian cancer cell lines, including nine with ‑mutations and five carrying ‑mutations, to olaparib and niraparib was determined and a subset of seven cell lines was selected to investigate the potential of olaparib to produce resistance. It was identified that escalating olaparib did neither produce subcells with acquired PARPi‑resistance nor did it produce acquired cross‑resistance to platinum compounds, doxorubicin, and paclitaxel. This finding was independent of the cells' and mutation status. CRISPR‑ mediated deletion of did not affect sensitivity to PARPi, platinum compounds, doxorubicin, and paclitaxel. In addition, olaparib sensitivity correlated with niraparib sensitivity, but ‑mutated cells were not more sensitive to PARPi. Moreover, PARPi sensitivity associated with cross‑sensitivity not only to platinum compounds but also to anthracylines, paclitaxel, and inhibitors of histone deacetylases. These data indicated that olaparib exposure is unlikely to produce an acquired resistance phenotype and that PARPi‑sensitive ovarian cancer cells are also cross‑sensitive to non‑platinum and even to compounds not directly interacting with the DNA.