Alex Goodwin, from Rugby, England, was diagnosed with Ewing’s Sarcoma last year after months of agony in his joints and muscles. He finished treatment earlier this month and is headed home in August.

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Ewing sarcoma is a pediatric cancer driven by EWS-ETS transcription factor fusion oncoproteins in an otherwise stable genomic background. The majority of tumors express wild-type TP53, and thus, therapies targeting the p53 pathway would benefit most patients. To discover targets specific for TP53 wild-type Ewing sarcoma, we used a genome-scale CRISPR-Cas9 screening approach and identified and validated MDM2, MDM4, USP7, and PPM1D as druggable dependencies. The stapled peptide inhibitor of MDM2 and MDM4, ATSP-7041, showed anti-tumor efficacy in vitro and in multiple mouse models. The USP7 inhibitor, P5091, and the Wip1/PPM1…

Source: The Journal of Experimental MedicineCategory: Internal Medicine Authors: Tags: Solid Tumors Articles Source Type: research

(Massachusetts General Hospital) A Massachusetts General Hospital research team has used epigenome editing tools to investigate how the genetic abnormality that drives Ewing sarcoma — the second most common bone cancer in children and young adults — unleashes tumor growth.

Dysregulation of repetitive elements has been implicated in many cancers and other human diseases; however, the role of repetitive elements remains largely unexplored. In this issue of Genes &Development, Boulay and colleagues (pp. 1008–1019) explore the ability of GGAA repeats to act as alternative enhancers activated by EWS-FLI1 in Ewing sarcoma and contribute to tumorigenesis. Using CRISPR-mediated epigenome editing, repression of EWS-FLI1 targeted microsatellite enhancers halted aberrant gene expression and impaired the growth of Ewing sarcoma xenografts in vivo. The study reveals the regulatory capacity of r…

Source: Genes and DevelopmentCategory: Genetics & Stem Cells Authors: Tags: Chromosome Dynamics and Nuclear Architecture, Chromatin and Gene Expression, Cancer and Disease Models Outlook Source Type: research

Various types of repetitive sequences are dysregulated in cancer. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 induces chromatin features typical of active enhancers at GGAA microsatellite repeats, but the function of these sites has not been directly demonstrated. Here, by combining nascent transcription profiling with epigenome editing, we found that a subset of GGAA microsatellite repeats is transcriptionally active in Ewing sarcoma and that silencing individual repeats abolishes local nascent transcription and leads to markedly reduced expression of putative target genes. Epigenome silencing of these repeat …

Source: Genes and DevelopmentCategory: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research

CONCLUSION: Health care delay among patients with a previous diagnosis was longer, and was probably associated with the time taken for to referral to cancer centers. Patients without a previous histopathological diagnosis had longer hospital delays, which could be associated with possible difficulties regarding demand and high-cost procedures. Despite limitations, this study helps provide initial knowledge about the healthcare pathway delays for patients with bone cancer inside several Brazilian hospitals.
PMID: 30075119 [PubMed – as supplied by publisher]

Source: Jornal de PediatriaCategory: Pediatrics Authors: Tags: J Pediatr (Rio J) Source Type: research

Renal Ewing sarcoma (RES) is an extremely rare disease. The standard treatment for this disease is lacking, and clinical experience needs to be accumulated. Here, we report a case of RES that rapidly developed to metastatic disease and was refractory to radiotherapy and chemotherapy; however, the case obtained a partial response based on Choi criteria by orally taking antiangiogenic drug apatinib. Our case suggests that apatinib may be a therapeutic option for RES.

Source: Anti-Cancer DrugsCategory: Cancer & Oncology Tags: Clinical Reports Source Type: research

Publication date: October 2018Source: Biomedicine &Pharmacotherapy, Volume 106Author(s): Lingping Kong, Xin Li, Hong Wang, Guangyao He, Anzhou TangAbstractThe incidence of nasopharyngeal carcinoma (NPC) in China is relatively higher than that throughout the rest of the world, and NPC is geographically distributed. Long non-coding RNA (lncRNA) plays a key role in the development of tumors. Recent studies have found that the lncRNA Ewing sarcoma-associated transcript 1 (EWSAT1) is highly expressed in various tumors and also in NPCs. The isoflavone calycosin, which is a typical Chinese herbal medicine, can inhibit the gro…

ConclusionThis paper has described population based measurements on burden and trends in incidence of skeletal Ewing in India. These may steer further research questions on the clinical and molecular epidemiology to explain factors associated with the increasing incidence of Ewing sarcoma bone observed in India.

ConclusionPediatric neck pain and/or torticollis should raise high suspicion for malignancy of cervical spine. Modern diagnostic means and techniques can assist in the screening and diagnosis of these tumors.

ConclusionThis paper has described population based measurements on burden and trends in incidence of skeletal Ewing in India. These may steer further research questions on the clinical and molecular epidemiology to explain factors associated with the increasing incidence of Ewing sarcoma bone observed in India.





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