Controversies and clinical unknowns in the use of PARP inhibitors in ovarian cancer

Abstract

Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have significantly improved the treatment of advanced ovarian cancer, however, there are still many aspects of their use that require further understanding. The optimal duration, timing and dosage of these agents and how to manage (oligo) progression occurring both during and following PARPi therapy are discussed. The evidence supporting their rechallenge, and how to overcome resistance are addressed. The long-term impacts of PARPi and monitoring patients during therapy are all important research themes to expand on.; PARP inhibitors: challenges and uncertainties within ovarian cancer PARP inhibitors are tablet medications used to treat ovarian cancer and have significantly improved the survival prospects of women with the disease, especially if they have a BRCA gene mutation. As their use has become more widespread, some challenges and uncertainties have emerged. These include the optimum length of time that these drugs should be used, both when used as treatment to prolong the response after first-line chemotherapy or to treat disease that has later progressed (relapsed) after chemotherapy. The degree of benefit of PARPi in patients without a BRCA mutation remains less clear. It is also not known whether PARPi could be beneficial if used before ovarian cancer surgery, and clinical studies are underway to assess this. While PARPi can be effective initially, many patients will develop resistance to these drugs, leading to relapse of their cancer. Proventing or overcoming this remains a key challenge. Re-use of the PARPi, when the amount of the disease at relapse is small, or re-using PARPi after radiotherapy or surgery, have been explored but the benefit is not yet clear. Similarly, combining the PARPI and another drug to prevent resistance is currently under investigation. The best way to monitor patients on PARPi for cancer relapse is also an area of uncertainty report. The full extent of long-term toxicities is becoming apparent as clinical studies report long-term data. Future research in ovarian cancer should focus on resolving ways to overcome the resistance associated with PARPi, developing more precise ways to select for those patients who would benefit most from their use. Addressing these challenges and unknowns will be important for optimising the use of PARPi in ovarian cancer treatment and further improving survival rates.