Clinical perspectives of BET inhibition in ovarian cancer
Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes...
Ausführliche Beschreibung
Autor*in: |
Andrikopoulou, Angeliki [verfasserIn] Liontos, Michalis [verfasserIn] Koutsoukos, Konstantinos [verfasserIn] Dimopoulos, Meletios-Athanasios [verfasserIn] Zagouri, Flora [verfasserIn] |
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Sprache: |
Englisch |
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2021 |
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Übergeordnetes Werk: |
Enthalten in: Cellular oncology - Amsterdam [u.a.] : IOS Press, 2004, 44(2021), 2 vom: 19. Jan., Seite 237-249 |
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Übergeordnetes Werk: |
volume:44 ; year:2021 ; number:2 ; day:19 ; month:01 ; pages:237-249 |
Links: |
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DOI / URN: |
10.1007/s13402-020-00578-6 |
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Katalog-ID: |
SPR043588972 |
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520 | |a Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. | ||
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650 | 4 | |a Epigenetic treatment |7 (dpeaa)DE-He213 | |
700 | 1 | |a Liontos, Michalis |e verfasserin |4 aut | |
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700 | 1 | |a Zagouri, Flora |e verfasserin |4 aut | |
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10.1007/s13402-020-00578-6 doi (DE-627)SPR043588972 (DE-599)SPRs13402-020-00578-6-e (SPR)s13402-020-00578-6-e DE-627 ger DE-627 rakwb eng 610 570 ASE Andrikopoulou, Angeliki verfasserin aut Clinical perspectives of BET inhibition in ovarian cancer 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. BET inhibitors (dpeaa)DE-He213 BET proteins (dpeaa)DE-He213 Bromodomain (dpeaa)DE-He213 Ovarian cancer (dpeaa)DE-He213 High-grade serous carcinoma (dpeaa)DE-He213 Epigenetic treatment (dpeaa)DE-He213 Liontos, Michalis verfasserin aut Koutsoukos, Konstantinos verfasserin aut Dimopoulos, Meletios-Athanasios verfasserin aut Zagouri, Flora verfasserin aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 44(2021), 2 vom: 19. Jan., Seite 237-249 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:44 year:2021 number:2 day:19 month:01 pages:237-249 https://dx.doi.org/10.1007/s13402-020-00578-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 44 2021 2 19 01 237-249 |
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10.1007/s13402-020-00578-6 doi (DE-627)SPR043588972 (DE-599)SPRs13402-020-00578-6-e (SPR)s13402-020-00578-6-e DE-627 ger DE-627 rakwb eng 610 570 ASE Andrikopoulou, Angeliki verfasserin aut Clinical perspectives of BET inhibition in ovarian cancer 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. BET inhibitors (dpeaa)DE-He213 BET proteins (dpeaa)DE-He213 Bromodomain (dpeaa)DE-He213 Ovarian cancer (dpeaa)DE-He213 High-grade serous carcinoma (dpeaa)DE-He213 Epigenetic treatment (dpeaa)DE-He213 Liontos, Michalis verfasserin aut Koutsoukos, Konstantinos verfasserin aut Dimopoulos, Meletios-Athanasios verfasserin aut Zagouri, Flora verfasserin aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 44(2021), 2 vom: 19. Jan., Seite 237-249 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:44 year:2021 number:2 day:19 month:01 pages:237-249 https://dx.doi.org/10.1007/s13402-020-00578-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 44 2021 2 19 01 237-249 |
allfields_unstemmed |
10.1007/s13402-020-00578-6 doi (DE-627)SPR043588972 (DE-599)SPRs13402-020-00578-6-e (SPR)s13402-020-00578-6-e DE-627 ger DE-627 rakwb eng 610 570 ASE Andrikopoulou, Angeliki verfasserin aut Clinical perspectives of BET inhibition in ovarian cancer 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. BET inhibitors (dpeaa)DE-He213 BET proteins (dpeaa)DE-He213 Bromodomain (dpeaa)DE-He213 Ovarian cancer (dpeaa)DE-He213 High-grade serous carcinoma (dpeaa)DE-He213 Epigenetic treatment (dpeaa)DE-He213 Liontos, Michalis verfasserin aut Koutsoukos, Konstantinos verfasserin aut Dimopoulos, Meletios-Athanasios verfasserin aut Zagouri, Flora verfasserin aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 44(2021), 2 vom: 19. Jan., Seite 237-249 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:44 year:2021 number:2 day:19 month:01 pages:237-249 https://dx.doi.org/10.1007/s13402-020-00578-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 44 2021 2 19 01 237-249 |
allfieldsGer |
10.1007/s13402-020-00578-6 doi (DE-627)SPR043588972 (DE-599)SPRs13402-020-00578-6-e (SPR)s13402-020-00578-6-e DE-627 ger DE-627 rakwb eng 610 570 ASE Andrikopoulou, Angeliki verfasserin aut Clinical perspectives of BET inhibition in ovarian cancer 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. BET inhibitors (dpeaa)DE-He213 BET proteins (dpeaa)DE-He213 Bromodomain (dpeaa)DE-He213 Ovarian cancer (dpeaa)DE-He213 High-grade serous carcinoma (dpeaa)DE-He213 Epigenetic treatment (dpeaa)DE-He213 Liontos, Michalis verfasserin aut Koutsoukos, Konstantinos verfasserin aut Dimopoulos, Meletios-Athanasios verfasserin aut Zagouri, Flora verfasserin aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 44(2021), 2 vom: 19. Jan., Seite 237-249 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:44 year:2021 number:2 day:19 month:01 pages:237-249 https://dx.doi.org/10.1007/s13402-020-00578-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 44 2021 2 19 01 237-249 |
allfieldsSound |
10.1007/s13402-020-00578-6 doi (DE-627)SPR043588972 (DE-599)SPRs13402-020-00578-6-e (SPR)s13402-020-00578-6-e DE-627 ger DE-627 rakwb eng 610 570 ASE Andrikopoulou, Angeliki verfasserin aut Clinical perspectives of BET inhibition in ovarian cancer 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. BET inhibitors (dpeaa)DE-He213 BET proteins (dpeaa)DE-He213 Bromodomain (dpeaa)DE-He213 Ovarian cancer (dpeaa)DE-He213 High-grade serous carcinoma (dpeaa)DE-He213 Epigenetic treatment (dpeaa)DE-He213 Liontos, Michalis verfasserin aut Koutsoukos, Konstantinos verfasserin aut Dimopoulos, Meletios-Athanasios verfasserin aut Zagouri, Flora verfasserin aut Enthalten in Cellular oncology Amsterdam [u.a.] : IOS Press, 2004 44(2021), 2 vom: 19. Jan., Seite 237-249 (DE-627)392964430 (DE-600)2158254-3 1875-8606 nnns volume:44 year:2021 number:2 day:19 month:01 pages:237-249 https://dx.doi.org/10.1007/s13402-020-00578-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 AR 44 2021 2 19 01 237-249 |
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Enthalten in Cellular oncology 44(2021), 2 vom: 19. Jan., Seite 237-249 volume:44 year:2021 number:2 day:19 month:01 pages:237-249 |
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Andrikopoulou, Angeliki @@aut@@ Liontos, Michalis @@aut@@ Koutsoukos, Konstantinos @@aut@@ Dimopoulos, Meletios-Athanasios @@aut@@ Zagouri, Flora @@aut@@ |
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BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. 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Clinical perspectives of BET inhibition in ovarian cancer |
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Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. |
abstractGer |
Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. |
abstract_unstemmed |
Background Bromodomain and extra-terminal (BET) proteins are epigenetic readers that bind to acetylated lysines of histones and regulate gene transcription. BET protein family members mediate the expression of various oncogenic drivers in ovarian cancer, such as the MYC and Neuregulin 1 (NRG1) genes. BRD4, the most thoroughly studied member of the BET family, is amplified in a significant subset of high-grade serous carcinomas (HGSC) of the ovary. It has been reported that BET inhibitors can attenuate the proliferation and dissemination of ovarian cancer cells by inhibiting oncogenic pathways, such as the FOXM1 and JAK/STAT pathways. BET inhibition can re-sensitize resistant ovarian cancer cells to already approved anticancer agents, including cisplatin and PARP inhibitors. This synergism was also confirmed in vivo in animal models. These and other preclinical results provide a promising basis for the application of BET inhibitors in ovarian cancer treatment. Currently, Phase I/II clinical trials explore the safety and efficacy profiles of BET inhibitors in various solid tumors, including ovarian tumors. Here, we review current knowledge on the molecular effects and preclinical activities of BET inhibitors in ovarian tumors. Conclusions BET proteins have emerged as new druggable targets for ovarian cancer. BET inhibitors may enhance antitumor activity when co-administered with conventional treatment regimens. Results from ongoing Phase I/II studies are anticipated to confirm this notion. |
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