Therapeutic applications of PARP inhibitors in ovarian cancer - 30/05/20
pages | 13 |
Iconographies | 3 |
Vidéos | 0 |
Autres | 0 |
Highlights |
• | PARPi are an effective therapeutic option for HR-deficient ovarian cancer patients. |
• | Chemotherapy-induced nerve impairment can be alleviated by PARPi. |
• | Resistance to PARPi is a huge barrier for long-term survival of patients. |
• | CRISPR and organoid are two novel technologies to select therapeutic target. |
• | PARPi combined with immunotherapy take an important place in future application. |
Abstract |
Ovarian cancer is the most lethal gynecologic malignancy with a high recurrence rate. Poly(ADP-ribose) polymerase inhibitors (PARPi) are one of the most active new therapies for treatment of ovarian cancer. These treatment modalities are based on the mechanisms of “synthetic lethal” and “PARP trapping”, especially for patients with homologous recombination deficiencies, and they demonstrate a high survival advantage. However, resistance to PARPi is an emerging problem. Identifying potential biomarkers to monitor the resistance and developing drug combination strategies are effective ways to address PARPi resistance. This review introduces the mechanisms of anticancer activity of PARPi and the developmental history in clinical research. Moreover, this paper systematically analyzes the functions of PARP family proteins. Additionally, this work highlights the treatment prospects of the combination of immunotherapy and PARPi in ovarian cancer. Finally, we propose several novel technologies to overcome the limitations of current preclinical studies and utilize them to select potential targets for combined drug therapy and identify biomarkers of PARPi resistance in ovarian cancer.
Le texte complet de cet article est disponible en PDF.Abbreviations : PARPi, CPB, EOC, DSB, HR, SL, ADPr, PAR, SSBs, NHEJ, HRR, HRD, DDR, PFS, HGSOC, CR, PR, ORR, DCR, 53BP1, SLFN11, TIGAR, PSROC, RR, invPFS, IQR, RP2D, DLT
Keywords : PARP inhibitor, Ovarian cancer, Resistance, Synthetic lethal, Combination therapy
Plan
Vol 127
Article 110204- juillet 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?