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Targeted therapies for advanced Ewing sarcoma family of tumors.

ABSTRACT: The prognosis of adolescent and young adult patients battling metastatic Ewing sarcoma family of tumors (ESFT) remains less than 30% despite the development of systemic therapies. In the era of personalized medicine, novel molecular targets have been tested in preclinical or clinical settings in ESFT. In this review, we focus on early clinical and translational research that identified multiple molecular targets, including IGF-1R; mTOR; tyrosine kinase inhibitors; EWS-FLI1-related targets, and others. Overall, novel targeted therapies demonstrated modest efficacy; however pronounced and durable antineoplastic responses have been observed in small subsets of treated patients, for example with IGF-1R antibodies. Identifying outcome-predicting biomarkers and overcoming treatment resistance remain major challenges. Due to the rarity of ESFT, multi-institutional collaboration efforts of clinicians, basic and translational scientists are needed in order to understand biology of therapeutic response or resistance, which can lead to development of novel therapeutic methods and improved patient outcomes.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC4426229 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Targeted therapies for advanced Ewing sarcoma family of tumors.

Jiang Yunyun Y Ludwig Joseph J Janku Filip F

Cancer treatment reviews 20150327 5

The prognosis of adolescent and young adult patients battling metastatic Ewing sarcoma family of tumors (ESFT) remains less than 30% despite the development of systemic therapies. In the era of personalized medicine, novel molecular targets have been tested in preclinical or clinical settings in ESFT. In this review, we focus on early clinical and translational research that identified multiple molecular targets, including IGF-1R; mTOR; tyrosine kinase inhibitors; EWS-FLI1-related targets, and o ...[more]

PMID: 25869102

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Project description:Purpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression. Results: Inflammatory genes are activated in ESFT patient samples, as 38 of 238 (16%) inflammatory genes were significantly upregulated (p<0.001) when compared to ESFT cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage related gene expression with 58 of 299 (19%) of these genes being upregulated (p<0.001). By combining expression data from ESFT patients, cell lines and muscle tissue samples we were able to identify a total of 32 presumptive inflammatory genes that characterize and distinguish tumour site in vivo from surrounding normal tissues. High expression of C5 correlated with better event free (p=0.01) and overall survival (p=0.004) in dose dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on tumor tissue microarray. Also, high expression of JAK1 correlated with favourable overall survival (p=0.04) and high expression of IL8, derived presumably from infiltrating immune cells, resulted in poor overall survival in Ewing sarcoma (p=0.04). Conclusions: Immune system related gene activation is observed in ESFT patient samples and several prognostically significant inflammatory genes (C5, JAK1 and IL8) for ESFT were identified. 44 Ewing sarcoma family of tumor patient and 11 cell line samples were analysed for their gene expression.

Dataset Information

Targeted therapies for advanced Ewing sarcoma family of tumors.

Publications

Targeted therapies for advanced Ewing sarcoma family of tumors.

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