Trabectedin for the treatment of soft tissue sarcomas

Sanctis, Rita De; Marrari, Andrea; Santoro, Armando

doi:10.1080/14656566.2016.1204295

Cited by 14 publications

(12 citation statements)

References 75 publications

(19 reference statements)

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“…This compound has shown a consistent activity in soft tissue sarcomas (STS) in several clinical trials. Although, it has not demonstrated an objective advantage over first-line standard doxorubicin-based therapy, trabectedin has been approved for the treatment of adult patients with advanced STS, after failure of anthracyclines and ifosfamide, or those who are unsuited to receive these agents [1], [7], [8]. Trabectedin presents a complex mechanism of action affecting several key processes in both tumor cells and microenvironment [8], [9], [10].…”

Section: Introductionmentioning

confidence: 99%

Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models

et al. 2017

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Trabectedin has been approved for second-line treatment of soft tissue sarcomas. However, its efficacy to target sarcoma initiating cells has not been addressed yet. Here, we used pioneer models of myxoid/round cell liposarcoma (MRCLS) and undifferentiated pleomorphic sarcoma (UPS) developed from transformed human mesenchymal stromal/stem cells (MSCs) to evaluate the effect of trabectedin in the cell type responsible for initiating sarcomagenesis and their derived cancer stem cells (CSC) subpopulations. We found that low nanomolar concentrations of trabectedin efficiently inhibited the growth of sarcoma-initiating cells, induced cell cycle arrest, DNA damage and apoptosis. Interestingly, trabectedin treatment repressed the expression of multiple genes responsible for the development of the CSC phenotype, including pluripotency factors, CSC markers and related signaling pathways. Accordingly, trabectedin induced apoptosis and reduced the survival of CSC-enriched tumorsphere cultures with the same efficiency that inhibits the growth of bulk tumor population. In vivo, trabectedin significantly reduced the mitotic index of MRCLS xenografts and inhibited tumor growth at a similar extent to that observed in doxorubicin-treated tumors. Combination of trabectedin with campthotecin (CPT), a chemotherapeutic drug that shows a robust anti-tumor activity when combined with alkylating agents, resulted in a very strong synergistic inhibition of tumor cell growth and highly increased DNA damage and apoptosis induction. Importantly, the enhanced anti-tumor activity of this combination was also observed in CSC subpopulations. These data suggest that trabectedin and CPT combination may constitute a novel strategy to effectively target both the cell-of-origin and CSC subpopulations in sarcoma.

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Section: Introductionmentioning

confidence: 99%

Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models

et al. 2017

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“…Though sarcomas are now histopathologically categorized, they have been also molecularly classified into different groups. The molecular advancement has improved the understanding of pathogenesis of soft-tissue sarcomas, as well as provided beneficial targets for clinical settings including diagnosis and treatments [ 13 – 19 ]. However, the pathogenesis of soft-tissue sarcomas is complex due to multiple molecular events being involved.…”

Section: Introductionmentioning

confidence: 99%

Prediction of clinical outcome and survival in soft-tissue sarcoma using a ten-lncRNA signature

Wei

Tang

et al. 2017

Oncotarget

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The prognostic value of long non-coding RNAs (lncRNAs) in patients with soft-tissue sarcoma has rarely been unraveled. The aim of the study was to find a lncRNA signature to predict the clinical outcome and survival in soft-tissue sarcoma based on the high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA) database. The lncRNAs which closely correlated with overall survival in 258 soft-tissue sarcoma patients were identified with Cox proportional regression model. Ten lncRNAs, including RP11-560J1.2, AP001432.14, RP4-665J23.1, LINC00680, AC006129.2, RP11-230G5.2, BACH1-IT2, RP11-274B21.9, RP11-504A18.1 and RP11-713P17.3, were selected to calculate a risk score. The risk score could effectively predict patients’ outcome, such as the status of mitotic count of tumor cells, person neoplasm cancer and residual tumor. More inspiringly, the risk score generated from the 10-lncRNA signature was an independent prognostic indicator for soft-tissue sarcoma patients. Overall, this 10-lncRNA signature gains the potential as an effective prognostic tool for soft-tissue sarcoma as part of the integrated clinical RNA-seq program.

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“…In recent years, natural anticancer drugs have received much attention, including Yondelis (trabectedin), a natural compound from the tunicate, Ecteinascidia turbinata , which has been used to treat soft-tissue sarcoma. 7 , 8 Terpenoids are a large and diverse class of natural compounds that occur widely in nature as a secondary metabolite of organisms, and are derived biosynthetically from units of isoprene. Among the terpenoids, triterpenes reportedly possess anti-inflammatory, antipyretic, and antitumor effects.…”

Section: Introductionmentioning

confidence: 99%

Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

Mori¹,

Shirai²,

Terauchi³

et al. 2017

OTT

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There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

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Trabectedin for the treatment of soft tissue sarcomas

Cited by 14 publications

References 75 publications

Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models

Trabectedin and Campthotecin Synergistically Eliminate Cancer Stem Cells in Cell-of-Origin Sarcoma Models

Prediction of clinical outcome and survival in soft-tissue sarcoma using a ten-lncRNA signature

Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

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