An Overview of PARP Resistance in Ovarian Cancer from a Molecular and Clinical Perspective
Epithelial ovarian cancer (EOC), a primarily high-grade serous carcinoma (HGSOC), is one of the major causes of high death-to-incidence ratios of all gynecological cancers. Cytoreductive surgery and platinum-based chemotherapy represent the main treatments for this aggressive disease. Molecular characterization of HGSOC has revealed that up to 50% of cases have a deficiency in the homologous recombination repair (HRR) system, which makes these tumors sensitive to poly ADP-ribose inhibitors (PARP-is). However, drug resistance often occurs and overcoming it represents a big challenge. A number of strategies are under investigation, with the most promising being combinations of PARP-is with antiangiogenetic agents and immune checkpoint inhibitors. Moreover, new drugs targeting different pathways, including the ATR-CHK1-WEE1, the PI3K-AKT and the RAS/RAF/MEK, are under development both in phase I and II-III clinical trials. Nevertheless, there is still a long way to go, and the next few years promise to be exciting.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
International journal of molecular sciences - 24(2023), 15 vom: 25. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cordani, Nicoletta [VerfasserIn] |
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| Links: |
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| Themen: |
Epithelial ovarian cancer |
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| Anmerkungen: |
Date Revised 14.08.2023 published: Electronic Citation Status Publisher |
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| doi: |
10.3390/ijms241511890 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM360687741 |
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| 520 | |a Epithelial ovarian cancer (EOC), a primarily high-grade serous carcinoma (HGSOC), is one of the major causes of high death-to-incidence ratios of all gynecological cancers. Cytoreductive surgery and platinum-based chemotherapy represent the main treatments for this aggressive disease. Molecular characterization of HGSOC has revealed that up to 50% of cases have a deficiency in the homologous recombination repair (HRR) system, which makes these tumors sensitive to poly ADP-ribose inhibitors (PARP-is). However, drug resistance often occurs and overcoming it represents a big challenge. A number of strategies are under investigation, with the most promising being combinations of PARP-is with antiangiogenetic agents and immune checkpoint inhibitors. Moreover, new drugs targeting different pathways, including the ATR-CHK1-WEE1, the PI3K-AKT and the RAS/RAF/MEK, are under development both in phase I and II-III clinical trials. Nevertheless, there is still a long way to go, and the next few years promise to be exciting | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PARP inhibitors | |
| 650 | 4 | |a epithelial ovarian cancer | |
| 650 | 4 | |a resistance | |
| 700 | 1 | |a Bianchi, Tommaso |e verfasserin |4 aut | |
| 700 | 1 | |a Ammoni, Luca Carlofrancesco |e verfasserin |4 aut | |
| 700 | 1 | |a Cortinovis, Diego Luigi |e verfasserin |4 aut | |
| 700 | 1 | |a Cazzaniga, Marina Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Lissoni, Andrea Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Landoni, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a Canova, Stefania |e verfasserin |4 aut | |
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