Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?
| Autor: | Nicholas Pavlidis, Peeter Karihtala, Mehmet Akif Ozturk, Afroditi Karathanasi, Stergios Boussios, Matin Sheriff, Eleftherios P. Samartzis, Elie El Rassy, George Pappas-Gogos, Mario Uccello, Michail Tringos, Michele Moschetta |
|---|---|
| Přispěvatelé: | University of Zurich, Department of Oncology, HUS Comprehensive Cancer Center, University of Helsinki, Helsinki University Hospital Area |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
EPITHELIAL OVARIAN Veliparib endocrine system diseases Poly ADP ribose polymerase 3122 Cancers 610 Medicine & health Synthetic lethality talazoparib Olaparib homologous recombination (HR) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Review Article on Ovarian Cancer: State of the Art and Perspectives of Clinical Research ADVANCED SOLID MALIGNANCIES Ovarian cancer ABDOMINAL RADIATION-THERAPY Medicine Talazoparib DOSE-ESCALATION breast cancer gene (BRCA) Rucaparib veliparib business.industry PRIMARY PERITONEAL JAPANESE PATIENTS VELIPARIB ABT-888 General Medicine medicine.disease 10174 Clinic for Gynecology 3. Good health FALLOPIAN-TUBE 030104 developmental biology PHASE-I ovarian cancer chemistry 030220 oncology & carcinogenesis OLAPARIB MAINTENANCE THERAPY Cancer research business poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) |
| Zdroj: | Ann Transl Med |
| Popis: | Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women, potentially due to ineffectiveness of screening tests for early detection. Patients typically present with advanced disease at diagnosis, whereas, up to 80% relapse and the estimated median progression-free survival (PFS) is approximately 12-18 months. Increased knowledge on the molecular biology of EOC resulted in the development of several targeted therapies, including poly(ADP-ribose) polymerase (PARP) inhibitors. These agents have changed the therapeutic approach of the EOC and exploit homologous recombination (HR) deficiency through synthetic lethality, especially in breast cancer genes 1 and 2 (BRCA1/2) mutation carriers. Furthermore, BRCA wild-type patients with other defects in the HR repair pathway, or those with platinum-resistant tumors may obtain benefit from this treatment. While PARP inhibitors as a class display many similarities, several differences in structure can translate into differences in tolerability and antitumor activity. Currently, olaparib, rucaparib, and niraparib have been approved by Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for the treatment of EOC, while veliparib is in the late stage of clinical development. Finally, since October 2018 talazoparib is FDA and EMA approved for BRCA carriers with metastatic breast cancers. In this article, we explore the mechanisms of DNA repair, synthetic lethality, efficiency of PARP inhibition, and provide an overview of early and ongoing clinical investigations of the novel PARP inhibitors veliparib and talazoparib. |
| Databáze: | OpenAIRE |
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