scholarly journals Current Status and Perspectives of Patient-Derived Models for Ewing’s Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2520
Author(s):  
Tadashi Kondo

Patient-derived cancer models, including cell lines, organoids, and xenografts, are indispensable tools in cancer research. These models, which recapitulate molecular features of original tumors, allow studies on the biological significance of cancer-associated genes, antitumor effects of novel agents, and molecular mechanisms underlying clinical behaviors of tumors. Moreover, the predictive utility of patient-derived cancer models is expected to facilitate drug development and precision medicine. Ewing’s sarcoma is a highly aggressive mesenchymal tumor with a high metastasis rate. Previous studies demonstrated the utility of cell lines and xenografts in Ewing’s sarcoma research and clinical studies. However, the number of Ewing’s sarcoma models available from public biobanks is limited; this creates an obstacle for research on Ewing’s sarcoma. Novel Ewing’s sarcoma models are needed to establish their utility, further our understanding of the molecular mechanisms, and help develop effective therapeutic strategies. In this review, the current status of patient-derived cancer models is overviewed, and future prospects of model development are discussed from the perspective of Ewing’s sarcoma research. It should be of interest to researchers and clinicians who work on patient-derived cancer models.

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e80060 ◽  
Author(s):  
William A. May ◽  
Rita S. Grigoryan ◽  
Nino Keshelava ◽  
Daniel J. Cabral ◽  
Laura L. Christensen ◽  
...  

2011 ◽  
Author(s):  
Cecilia Garofalo ◽  
Maria Cristina Manara ◽  
Maria Teresa Marino ◽  
Pier Luigi Lollini ◽  
Piero Picci ◽  
...  

2020 ◽  
Vol 21 (12) ◽  
pp. 4460 ◽  
Author(s):  
Josephine M. Jacoby ◽  
Silas Strakeljahn ◽  
Andreas Nitsch ◽  
Sander Bekeschus ◽  
Peter Hinz ◽  
...  

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.


2007 ◽  
Vol 103 (4) ◽  
pp. 1344-1354 ◽  
Author(s):  
Cristina Zanini ◽  
Giuliana Giribaldi ◽  
Giorgia Mandili ◽  
Franco Carta ◽  
Nicoletta Crescenzio ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1553
Author(s):  
Ellie Esfandiari Nazzaro ◽  
Fahad Y. Sabei ◽  
Walter K. Vogel ◽  
Mohamad Nazari ◽  
Katelyn S. Nicholson ◽  
...  

Ewing’s sarcoma, characterized by pathognomonic t (11; 22) (q24; q12) and related chromosomal ETS family translocations, is a rare aggressive cancer of bone and soft tissue. Current protocols that include cytotoxic chemotherapeutic agents effectively treat localized disease; however, these aggressive therapies may result in treatment-related morbidities including second-site cancers in survivors. Moreover, the five-year survival rate in patients with relapsed, recurrent, or metastatic disease is less than 30%, despite intensive therapy with these cytotoxic agents. By using high-throughput phenotypic screening of small molecule libraries, we identified a previously uncharacterized compound (ML111) that inhibited in vitro proliferation of six established Ewing’s sarcoma cell lines with nanomolar potency. Proteomic studies show that ML111 treatment induced prometaphase arrest followed by rapid caspase-dependent apoptotic cell death in Ewing’s sarcoma cell lines. ML111, delivered via methoxypoly(ethylene glycol)-polycaprolactone copolymer nanoparticles, induced dose-dependent inhibition of Ewing’s sarcoma tumor growth in a murine xenograft model and invoked prometaphase arrest in vivo, consistent with in vitro data. These results suggest that ML111 represents a promising new drug lead for further preclinical studies and is a potential clinical development for the treatment of Ewing’s sarcoma.


2020 ◽  
Author(s):  
Christian Marx ◽  
Marc U. Schaarschmidt ◽  
Joanna Kirkpatrick ◽  
Lisa Marx-Blümel ◽  
Doerte Hoelzer ◽  
...  

Abstract Introduction: Ewing's sarcoma is an aggressive childhood malignancy whose outcome has not substantially improved over the last two decades. In this study, combination treatments of the HSP90 inhibitor AUY922 with either the ATR inhibitor VE821 or the ATM inhibitor KU55933 were investigated for their effectiveness in Ewing's sarcoma cells.Methods: Effects were determined in p53 wild-type and p53 null Ewing's sarcoma cell lines by flow cytometric analyses of cell death, mitochondrial depolarization and cell-cycle distribution. They were molecularly characterized by gene and protein expression profiling, and by quantitative whole proteome analysis.Results: AUY922 alone induced DNA damage, apoptosis and ER stress, while reducing the abundance of DNA repair proteins. The combination of AUY922 with VE821 led to strong apoptosis induction independent of the cellular p53 status, yet based on different molecular mechanisms. p53 wild-type cells activated pro-apoptotic gene transcription and underwent mitochondria-mediated apoptosis. p53 null cells, however, accumulated higher levels of DNA damage, ER stress and autophagy, eventually leading to apoptosis. Impaired PI3K/AKT/mTOR signaling further contributed to the antineoplastic combination effects of AUY922 and VE821 in p53 null cells. In contrast, the combination of AUY922 with KU55933 did not produce a cooperative effect.Conclusion: Our study reveals that HSP90 and ATR inhibitor combination treatment may be an effective therapeutic approach for Ewing's sarcoma irrespective of the p53 status.


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