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Currently Approved Poly (Adenosine Diphosphate-Ribose) Inhibitors in Ovarian Cancer: Current Status and Future Directions

[ Vol. 5 , Issue. 1 ]

Author(s):

Gonzalo H. Giornelli and Pablo Mando*   Pages 3 - 12 ( 10 )

Abstract:


Background: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors have entered into the clinic rapidly and are becoming a powerful therapeutic tool, especially in the management of BRCA associated ovarian cancers. PARP inhibitors have exploited the homologous recombination deficiency, present in up to 50% of ovarian cancers, through synthetic lethality: A novel therapeutic approach to this disease.

Objective: Through an extensive review of PARP inhibitors we evaluated the existing evidence in the clinical trial as monotherapy and combined with chemotherapy in ovarian cancer.

Conclusion: PARP inhibitors have demonstrated to fulfill the characteristics of the ideal maintenance therapy agent. Understanding biomarkers in this scenario holds maximum importance to allow its foreseen potential, although “platinum-sensitivity” shows to be a “functional biomarker”, reflecting a homologous recombination deficiency phenotype, thus, proving sensitivity to PARP inhibitors. Many clinical studies are ongoing marking its future directions and analyzing its effect on several combinations. Numerous questions remain unanswered, such as mechanisms of resistance or sequential use, and need to be explored completely through ongoing research.

Keywords:

Ovarian cancer, PARP inhibitors, homologous recombination deficiency, synthetic lethality, polymerase inhibitors, disease free survival.

Affiliation:

Instituto Alexander Fleming, Buenos Aires, Oncology Department, CEMIC, Buenos Aires

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