A Review of Ewing Sarcoma Treatment: Is it Still a Subject of Debate?

Kridis, Wala Ben; Toumi, Nabil; Chaari, H.; Khanfir, Afef; K, Ayadi; Keskes, Hassib; Boudawara, Tahia; Daoud, J.; Frikha, M.

doi:10.2174/1574887112666170120100147

Cited by 35 publications

(35 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For these patients, outcome is rather poor with a long-term survival rate of around 25% [6][7][8], with a slightly better survival rate for patients exhibiting exclusively lung metastases [9,10]. Nevertheless, patients with localized (i.e., non-metastatic) disease can be effectively treated with combined chemotherapy and surgery [11][12][13], resulting in a long-term survival rate of more than 70% [14][15][16]. Besides metastasis, larger tumor size also correlates negatively with patients' overall survival [8].…”

Section: Introductionmentioning

confidence: 99%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

View full text Add to dashboard Cite

Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.

show abstract

Section: Introductionmentioning

confidence: 99%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…However, despite significant progress regarding intensive chemotherapy and improvements in the outcomes of patients with localized ES, relapse after initial clinical remission is not uncommon, and the overall survival for patients with relapsed or metastatic ES remains less than 20% [ 1 , 3 – 8 ]. Therefore, the development of novel therapeutic targets that inhibit biological pathways known to contribute to ES growth and malignant behavior is essential.…”

Section: Introductionmentioning

confidence: 99%

IRE1α-XBP1 inhibitors exerted anti-tumor activities in Ewing’s sarcoma

et al. 2018

View full text Add to dashboard Cite

Ewing's sarcoma (ES) is the second-most frequent pediatric bone tumor. Chromosomal translocation t(11;22)(q24:q12) results in the formation of EWS/FLI1 gene fusion, which is detected in approximately 90% of tumors of the Ewing family. Several transcriptome studies have provided lists of genes associated with EWS/FLI1 expression. However, the protein expression profiles associated with EWS/FLI1 have yet to be elucidated. In this study, to identify the regulated proteins associated with EWS/FLI1 and therapeutic targets in ES, we conducted proteomic studies using EWS/FLI1 knockdown in four Ewing's sarcoma cell lines and human mesenchymal stem cells (hMSCs) expressing EWS/FLI1. Isobaric tags for relative and absolute quantitation (i-TRAQ) analyses identified more than 2,000 proteins regulated by the EWS/FLI1 fusion. In addition, the network analyses identified several critical pathways, including XBP1, which was ranked the highest. XBP1 is a protein well known to play an important role in the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress through the IRE1α-XBP1 pathway. We confirmed the high mRNA expression of XBP1 (spliced XBP1 and unspliced XBPl) in surgical samples and cell lines in ES. The silencing of XBP1 significantly suppressed the cell viabilities in ES cell lines. In the inhibitor assays using IRE1α-XBP1 inhibitors, including toyocamycin, we confirmed that these agents significantly suppressed the cell viabilities, leading to apoptosis in ES cells both in vitro and in vivo. Our findings suggested that IRE1α-XBP1 inhibitors might be useful for developing novel therapeutic strategies in ES.

show abstract

“…In the literature, the role of extensive and complete or near complete surgical excision has been advocated as critical for local tumor control and prolonged survival 5,21,22 , which was corroborated by our results. Retrospective analysis of several large groups gives the impression of maximal local control when surgery is feasible 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Topotecan plus cyclophosphamide and temozolomide plus irinotecan are most commonly used. Gemcitabine plus docetaxel and high-dose ifosfamide have also been used in this context, with variable results 23 . Our data supported the role of chemotherapy as a beneficial component in the multimodal treatment of peripheral PNET.…”

Section: Discussionmentioning

confidence: 99%

Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor

Liu

Yuan

Zhang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.

show abstract

A Review of Ewing Sarcoma Treatment: Is it Still a Subject of Debate?

Abstract: The treatment of ES includes neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The role of high-dose chemotherapy is still debated.

Cited by 35 publications

References 1 publication

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

IRE1α-XBP1 inhibitors exerted anti-tumor activities in Ewing’s sarcoma

Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor

Contact Info

Product

Resources

About