Investigational PARP inhibitors for the treatment of biliary tract cancer : spotlight on preclinical and clinical studies
Introduction: Alterations in DNA damage repair (DDR) genes are observed in up to 60% of biliary tract cancer (BTC) patients. Patients with advanced/metastatic BTC have few therapeutic options, so there is a demand for the development of new and innovative treatment approaches. The use of poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors (PARPis), either as a monotherapy or in combination, is being extensively studied in clinical trials.Areas Covered: This review examines the targeting of the DDR pathway with PARPis as a potential novel treatment option for the management of BTCs. The rationale behind the use of PARPis and current clinical experience is discussed. Moreover, further insights into potential future directions concerning the applicability of PARPis in the treatment of BTCs are proposed.Expert Opinion: Prospective clinical data with PARPis in the treatment of BTCs are limited. The potential combination of PARPis and IDH1 inhibitors or immune checkpoint inhibitors in clinical trials is interesting because of the potential synergistic preclinical data. There are other possible combinations including those drugs that target the angiogenesis or STAT3 pathways. An enhanced understanding of acquired resistance to PARPis is necessary to progress the use of these agents in clinical trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Expert opinion on investigational drugs - 30(2021), 4 vom: 03. Apr., Seite 451-461 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mehta, Rutika [VerfasserIn] |
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| Links: |
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| Themen: |
Biliary tract tumors |
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| Anmerkungen: |
Date Completed 12.05.2021 Date Revised 12.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/13543784.2021.1898586 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32218021X |
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| 500 | |a Date Revised 12.05.2021 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Introduction: Alterations in DNA damage repair (DDR) genes are observed in up to 60% of biliary tract cancer (BTC) patients. Patients with advanced/metastatic BTC have few therapeutic options, so there is a demand for the development of new and innovative treatment approaches. The use of poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors (PARPis), either as a monotherapy or in combination, is being extensively studied in clinical trials.Areas Covered: This review examines the targeting of the DDR pathway with PARPis as a potential novel treatment option for the management of BTCs. The rationale behind the use of PARPis and current clinical experience is discussed. Moreover, further insights into potential future directions concerning the applicability of PARPis in the treatment of BTCs are proposed.Expert Opinion: Prospective clinical data with PARPis in the treatment of BTCs are limited. The potential combination of PARPis and IDH1 inhibitors or immune checkpoint inhibitors in clinical trials is interesting because of the potential synergistic preclinical data. There are other possible combinations including those drugs that target the angiogenesis or STAT3 pathways. An enhanced understanding of acquired resistance to PARPis is necessary to progress the use of these agents in clinical trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Cholangiocarcinoma | |
| 650 | 4 | |a DDR alterations | |
| 650 | 4 | |a PARP inhibitors | |
| 650 | 4 | |a biliary tract tumors | |
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| 700 | 1 | |a Yu, James |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Richard |e verfasserin |4 aut | |
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