**5. Conclusion**

The main objective of this chapter was to highlight the recent contribution brought by the approval of PARPis for the treatment of advanced EOC. The PARPis clinical development underscored the value of the "bench to bedside framework" which translates basic biological knowledge into medical therapeutic application.

Initially developed as maintenance therapy in patients with complete or partial response after platinum-based chemotherapy in a recurrent setting, PARPi is now approved in multiple settings including as a frontline management strategy. However, the use of these novel agents early in the disease trajectory exposes new therapeutic challenges associated with PARPi-resistance which clinically leads to treatment failure. As a result, uncovering the molecular mechanisms linked to acquired and intrinsic resistance to PARPi is an active area of research. Overall increased drug efflux (which leads to reduced intracellular drug concentrations), restoration of HRR repair (re-expression of functional proteins involved in HRR or somatic reversion mutations in either *BRCA1* or *BRCA*2), and aberrations in PARP signaling are the common pathways involved in PARPi-resistance [76]. A detailed elucidation of these molecular events would be essential for the design of new therapeutic strategies to prevent/ overcome resistance. Currently, several hypotheses within clinical trials (targeted combination intervention) are under investigation with the aim to re-sensitize and enhance ovarian cancer cells to PARPis, while optimizing tolerability and quality of life. The hope is that there will be a continuous improvement in targeted therapies leading to an extension of overall survival and an effective curability of this disease.
