Expression of therapeutic targets in Ewing sarcoma family tumors

Ahmed, Atif; Sherman, Ashley; Pawel, Bruce

doi:10.1016/j.humpath.2011.09.001

Cited by 17 publications

(14 citation statements)

References 39 publications

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“…ES expresses mTOR [106], and has an upregulated phosphorylation of mTOR [107]. The effects of mTOR inhibitors on ES have been investigated.…”

Section: Targeted Therapymentioning

confidence: 99%

Potential approaches to the treatment of Ewing's sarcoma

Guo

et al. 2016

Oncotarget

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Ewing’s sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.

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“…ES expresses mTOR [106], and has an upregulated phosphorylation of mTOR [107]. The effects of mTOR inhibitors on ES have been investigated.…”

Section: Targeted Therapymentioning

confidence: 99%

Potential approaches to the treatment of Ewing's sarcoma

Guo

et al. 2016

Oncotarget

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“…prognostic carcinomas was tested and specifi detection [3 . In colorectal and predictiv s, gastrointestin before [4,5,10,1 ic monoclonal 3] , for potential n 41 high-grade he presence of ases by IHC w Therefore, thes biomarker for t tation is a rare les with positiv aining (A) melanoma is omas, BRAF m [8] . The mutati mors, ovarian a een widely stu 1) [3,7,9] agains py [7] .…”

Section: Discmentioning

confidence: 99%

“…A few studies have also been done in sarcomas. Ahmed et al found no expression of BRAF in 72 Ewing family tumors [4] , and Cipriani et al [5] evaluated 104 tumors, including 90 sarcomas, with no BRAF mutation identified in the sarcoma group. On the other hand, Shukla et al [6] identified BRAF mutations in 1.3% of Ewing sarcomas and 1.7% of embryonal rhabdomyosarcomas.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical study of BRAF V600E mutant protein expression in high-grade sarcomas

Valente

Whiting²,

Tull

et al. 2015

JST

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BRAF V600E is a mutation present in numerous neoplasms, including melanomas, thyroid, colorectal and ovarian carcinomas, gastrointestinal stromal tumors, and Langerhans' cell histiocytosis. Vemurafenib, a BRAF V600E kinase inhibitor has been successfully used in the treatment of melanoma. The role of this mutation in unclassified high-grade sarcomas, malignancies with very limited treatment options, has not been widely studied. Because of the availability of a highly sensitive and specific antibody (VE1) against the BRAF V600E mutant protein, we tested 48 cases of unclassified high-grade sarcomas. Cytoplasmic expression intensity was graded as negative (0), or positive (2+ or 3+) by two pathologists and a pathology resident. Forty one out of 48 specimens remained intact in the cores after immunohisto chemistry (IHC) processing. Six of the 41 cases (15%) were scored as positive. In addition, non-specific nuclear staining was detected in 12/88 cores (14%). The 6 positive cases were tested for the BRAF V600E mutation by RT-PCR, and all were negative. Based on these results, we concluded that BRAF V600E mutation is rare in unclassified high-grade sarcomas, and because of the non-specific staining, results should be interpreted with caution.

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“…28-31 While IGF-1R, EGFR, and mTOR are all potential drug targets, it is yet to be fully determined if inhibition of any of these pathways can be augmented by simultaneously targeting other pathways. 32,33 The ability to quantify pathway components and establish clinically relevant levels will be important to determine how the expression of these proteins drive tumor growth, survival and drug sensitivity. Ultimately, finding the optimal targeted strategy for an individual patient may be informed by studies quantifying protein expression in that individual's tumor.…”

Section: Discussionmentioning

confidence: 99%