ArticleJournal of hematology & oncology2017
Activity of trabectedin and the PARP inhibitor rucaparib in soft-tissue sarcomas.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- A Phase II Multicenter Trial of Trabectedin in Combination with Olaparib in Patients with Advanced Unresectable or Metastatic Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Trabectedin Induces Synthetic Lethality via the p53-Dependent Apoptotic Pathway in Ovarian Cancer Cells Without BRCA Mutations When Used in Combination with Niraparib.International journal of molecular sciences · 2025Article
- Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Trabectedin may be a valuable treatment option for elderly patients with metastatic soft tissue sarcomas.Frontiers in oncology · 2024Article
- Molecular landscape and therapeutic alterations in Asian soft-tissue sarcoma patients.Cancer medicine · 2022Article
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- Molecular signatures of BRCAness analysis identifies PARP inhibitor Niraparib as a novel targeted therapeutic strategy for soft tissue Sarcomas.Theranostics · 2020Article
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- PARP1 expression in soft tissue sarcomas is a poor-prognosis factor and a new potential therapeutic target.Molecular oncology · 2019Article
- Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?La Radiologia medica · 2019Review
- Precision Oncology in Sarcomas: Divide and Conquer.JCO precision oncology · 2019Review
- Overexpression of CLC-3 is regulated by XRCC5 and is a poor prognostic biomarker for gastric cancer.Journal of hematology & oncology · 2018Article
- Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model.BMC cancer · 2018Article
- Preclinical evaluation of the Aurora kinase inhibitors AMG 900, AZD1152-HQPA, and MK-5108 on SW-872 and 93T449 human liposarcoma cells.In vitro cellular & developmental biology. Animal · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrabectedin has recently been approved in the USA and in Europe for advanced soft-tissue sarcoma patients who have been treated with anthracycline-based chemotherapy without success. The mechanism of action of trabectedin depends on the status of both the nucleotide excision repair (NER) and homologous recombination (HR) DNA repair pathways. Trabectedin results in DNA double-strand breaks. We hypothesized that PARP-1 inhibition is able to perpetuate trabectedin-induced DNA damage.
methodsWe explored the effects of combining a PARP inhibitor (rucaparib) and trabectedin in a large panel of soft-tissue sarcoma (STS) cell lines and in a mouse model of dedifferentiated liposarcoma.
resultsThe combination of rucaparib and trabectedin in vitro was synergistic, inhibited cell proliferation, induced apoptosis, and accumulated in the G2/M phase of the cell cycle with higher efficacy than either single agent alone. The combination also resulted in enhanced γH2AX intranuclear accumulation as a result of DNA damage induction. In vivo, the combination of trabectedin and rucaparib significantly enhanced progression-free survival with an increased percentage of tumor necrosis.
conclusionThe combination of PARP inhibitor and trabectedin is beneficial in pre-clinical models of soft-tissue sarcoma and deserves further exploration in the clinical setting.
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