Poly (ADP-ribose) polymerase inhibitors (PARPi) have emerged as a promising therapeutic approach in the treatment of various cancers, particularly those with deficiencies in DNA repair mechanisms. However, the clinical efficacy of PARPi is often limited by the development of resistance, which poses a significant challenge to their long-term use. Elucidating the molecular mechanisms underlying PARPi resistance is crucial for developing novel therapeutic agents and strategies to overcome this resistance and optimize patient treatment regimens.

Olaparib-resistant MDA-MB-436 breast cancer cell line was generated through prolonged in vitro exposure to escalating doses of Olaparib. In vitro and in vivo efficacy studies were conducted to validate the resistance to Olaparib.

The MDA-MB-436-R-Olaparib model exhibited robust drug tolerance both in vitro and in vivo, with cross-resistance to other PARP inhibitors. Notably, cell viability assays revealed that the MDA-MB-436-R-Olaparib cells had reduced sensitivity to cisplatin compared to parental MDA-MB-436 cells.

In summary, this Olaparib-resistant model facilitates a systematic investigation of PARPi resistance mechanisms and discovery of combinatorial therapeutic strategies.