Poly(ADP-ribose) polymerase inhibitors in Ewing sarcoma
PURPOSE OF REVIEW: In 2012, two publications revealed a particular sensitivity of Ewing sarcoma cells to the inhibition of poly(ADP-ribose) polymerase (PARP). This review updates the reader on PARP function, the development of PARP inhibitors (PARPi) and the evidence for targeting PARP in Ewing sarcoma. It concludes with a description of ongoing/emerging PARPi clinical trials in patients with Ewing sarcoma.
RECENT FINDINGS: PARP has a major role in DNA repair, and is a transcription regulator. The oncoprotein in Ewing sarcoma, EWS-FLI1, is proposed to interact with PARP-1, driving PARP-1 expression, which further promotes transcriptional activation by EWS-FLI1. Thus, there are two rationales for PARPi in the treatment of Ewing sarcoma: to disrupt the interaction between EWS-FLI1 and PARP, and for chemo-potentiation or radio-potentiation. The first clinical trial with a single agent PARPi failed to show significant responses, but preclinical evidence for combinations of PARPi with chemotherapy or radiotherapy is very promising.
SUMMARY: Despite initial excitement for the potential of PARPi as single agent therapy in Ewing sarcoma, the emerging preclinical data now strongly support testing PARPi in combination with chemo/radiotherapy clinically.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Current opinion in oncology - 26(2014), 4 vom: 19. Juli, Seite 428-33 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vormoor, Britta [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 04.02.2015 Date Revised 11.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/CCO.0000000000000091 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM238366863 |
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| 520 | |a PURPOSE OF REVIEW: In 2012, two publications revealed a particular sensitivity of Ewing sarcoma cells to the inhibition of poly(ADP-ribose) polymerase (PARP). This review updates the reader on PARP function, the development of PARP inhibitors (PARPi) and the evidence for targeting PARP in Ewing sarcoma. It concludes with a description of ongoing/emerging PARPi clinical trials in patients with Ewing sarcoma | ||
| 520 | |a RECENT FINDINGS: PARP has a major role in DNA repair, and is a transcription regulator. The oncoprotein in Ewing sarcoma, EWS-FLI1, is proposed to interact with PARP-1, driving PARP-1 expression, which further promotes transcriptional activation by EWS-FLI1. Thus, there are two rationales for PARPi in the treatment of Ewing sarcoma: to disrupt the interaction between EWS-FLI1 and PARP, and for chemo-potentiation or radio-potentiation. The first clinical trial with a single agent PARPi failed to show significant responses, but preclinical evidence for combinations of PARPi with chemotherapy or radiotherapy is very promising | ||
| 520 | |a SUMMARY: Despite initial excitement for the potential of PARPi as single agent therapy in Ewing sarcoma, the emerging preclinical data now strongly support testing PARPi in combination with chemo/radiotherapy clinically | ||
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